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81.
Hecker Markus Hollert Henner Cooper Ralph Vinggaard Anne-Marie Akahori Yumi Murphy Margaret Nellemann Christine Higley Eric Newsted John Wu Rudolph Lam Paul Laskey John Buckalew Angela Grund Stefanie Nakai Makoto Timm Gary Giesy John 《Environmental science and pollution research international》2007,14(1):23-30
Background, Goals and Scope In response to concerns that have been raised about chemical substances that may alter the function of endocrine systems and
result in adverse effects on human health, an OECD initiative was undertaken to develop and validate in vitro and in vivo assays to identify chemicals that may interfere with endocrine systems of vertebrates. Here we report on studies that were
conducted to develop and standardize a cell-based screening assay using the H295R cell line to prioritize chemicals that may
act on steroidogenic processes in humans and wildlife. These studies are currently ongoing as part of the ‘Special Activity
on the Testing and Assessment of Endocrine Disruptors’ within the OECD Test Guidelines Program to review, develop, standardize,
and validate a number of in vitro and in vivo toxicological assays for testing and assessment of chemicals concerning their potential to interact with the endocrine system
of vertebrates.
Study Design Six laboratories from five countries participated in the pre-validation studies. Each laboratory tested the effects of three
model chemicals on the production of testosterone (T) and estradiol (E2) using the H295R Steroidogenesis Assay. Chemicals
tested were well described inducers or inhibitors of steroidogenic pathways (forskolin, prochloraz and fadrozole). All experiments
were conducted in 24 well plates following standard protocols. Six different doses per compound were analyzed in triplicate
per plate. A quality control (QC) plate was run in conjunction with the chemical exposure plate to account for inter-assay
variation. Each chemical exposure was conducted two or three times.
Results All laboratories successfully detected increases and/or decreases in hormone production by H295R cells after exposure to the
different model compounds and there was good agreement in the pattern of response for all groups. Forskolin increased both
T and E2 while fadrozole and prochloraz decreased production of both hormones. All chemicals affected hormone production in
a dose-dependent manner with the exception of fadrozole which caused maximum inhibition of E2 at the two least concentrations
tested. Some inter-laboratory differences were noted in the alteration of hormone production measured in chemically exposed
cells. However, with the exception of the production of T measured at one laboratory in cells exposed to forskolin, the EC50s calculated were comparable (coefficients of variation 34–49%) for all hormones.
Discussion and Perspectives The results indicated that the H295R Steroidogenesis Assay protocol was robust, transferable and reproducible among all laboratories.
However, in several instances that were primarily related to one laboratory there were unexplained minor uncertainties related
to the inter-laboratory hormone production variation. Based on the findings from this Phase 2 prevalidation study, the H295R
Steroidogenesis Assay protocol is currently being refined. The next phase of the OECD validation program will test the refined
protocol among the same group of laboratories using an extended set of chemicals (∼30) that will include positive and negative
chemical controls as well as a broad spectrum of different potential inducers and inhibitors of steroidogenic pathways.
Submission Editor: Dr. Carsten Brühl (bruehl@uni-landau.de) 相似文献
82.
John P. Newnham M.R.C.O.G. John V. Crues III Arnold L. Vinstein Arnold L. Medearis 《黑龙江环境通报》1984,4(6):467-471
A case of prenatal sonographic detection of a posterior mediastinal cyst in an otherwise normal fetus is presented. Following surgical excision 5 days after birth, histological examination confirmed the cyst to be gastroenteric. The differential diagnosis and clinical value of prenatal detection are discussed. 相似文献
83.
《黑龙江环境通报》1986,6(6):451-456
The occasion of the 18th symposium of the European Society of Human Genetics, 20 May to 2 June, provided an opportunity for the WHO to sponsor a small meeting on the progress of risk evaluation in three large programmes of chorionic villus sampling (CVS). Their pooled information showed a rate of fetal loss of 3·4 per cent in the first 300 cases in each programme, falling to 1·7 per cent in the following 400 cases. 相似文献
84.
Thirty-two pregnancies (11 primi- and 21 multi-gravid) with an abnormal fetus were terminated between 16 and 35 weeks (mean 22 weeks; median 20 weeks) and a continuous intravenous infusion of 1 μg of the prostaglandin analogue sulprostone. All pregnancies were terminated vaginally, 31 of them with this regimen in a median induction-expulsion interval of 23 h (range 8–52 h). Complete expulsion of the placenta occurred in 72 per cent of cases. Median blood loss was 100 ml (range 20–2000 ml). There were only a few side-effects. We conclude that this induction regimen is both appropriate and safe for pregnancy termination in cases of fetal anomaly. 相似文献
85.
Ioxynil, a phenolic herbicide, is known to exert thyroid hormone (TH) disrupting activity by interfering with TH-binding to plasma proteins and a step of the cellular TH-signaling pathway in restricted animal species. However, comparative studies are still lacking on the TH disruption.We investigated the interaction of [125I]ioxynil with serum proteins from rainbow trout, bullfrog, chicken, pig, rat, and mouse, using native polyacrylamide gel electrophoresis. Candidate ioxynil-binding proteins, which included lipoproteins, albumin and transthyretin (TTR), differed among the vertebrates tested. Rainbow trout and bullfrog tadpole serum had the lowest binding activity for ioxynil, whereas the eutherian serum had the highest binding activity. The cellular uptake of, and response to, ioxynil were suppressed by rat serum greater than by tadpole serum. The cellular uptake of [125I]ioxynil competed strongly with phenols with a single ring, but not with THs. Our results suggested that ioxynil interferes with TH homeostasis in plasma and with a step of cellular TH-signaling pathway other than TH-uptake system, in a species-specific manner. 相似文献
86.
Xiaofei Qin Xijuan Xi Zhongzhi Yang Shishuai Yan Yaxian Zhao Rongguo Wei Yan Li Mi Tian Xingru Zhao Zhanfen Qin Xiaobai Xu 《环境科学学报(英文版)》2010,22(5):744-751
Decabromodiphenyl ether (decaBDE), as a flame retardant, is widely produced and used. To study the thyroid disruption by technical
decaBDE at low concentrations, Xenopus laevis tadpoles were exposed to technical decaBDE mixture DE-83R (1–1000 ng/L) in
water from stage 46/47 (free swimming larvae, system of Nieuwkoop and Faber) to stage 62. DE-83R at concentration of 1000 ng/L
significantly delayed the time to metamorphosis (presented by forelimb emergence, FLE). Histological examination showed that DE-
83R at all tested concentrations caused histological alterations – multilayer follicular epithelial cell and markedly increased follicle size
accompanied by partial colloid depletion and increase in the peripheral colloid vacuolation, in thyroid glands. All tested concentrations
of DE-83R also induced a down-regulation of thyroid receptor mRNA expression. These results demonstrated that technical decaBDE
disrupted the thyroid system in X. laevis tadpoles. Analysis of polybrominated diphenyl ethers (PBDEs) (sum of 39 congeners) in X.
laevis indicated that mean concentrations of total PBDEs in X. laevis exposed to 1, 10, 100, 1000 ng/L were 11.0, 128.1, 412.1, 1400.2
ng/g wet weight, respectively. Considering that PBDEs burden of X. laevis tadpoles was close to PBDEs levels in amphibians as reported
in previous studies, our study has raised new concerns for thyroid disruption in amphibians of technical decaBDE at environmentally
relevant concentrations. 相似文献
87.
88.
89.
内分泌干扰物三丁基锡诱导的腹足纲动物性畸变现象 总被引:9,自引:0,他引:9
论述了腹足纲雌性动物由于三丁基锡化合物的内分泌扰乱作用而诱发性畸变的现状.介绍了性畸变现象的发生过程,说明了普遍采用的腹足纲动物采集方式与生物样品中有机锡含量的分析方法.通过相对阴茎尺寸指数(RPSI)与输精管序列指数(VDS)两个概念给出了性畸变腹足纲动物的身体形态发生的变化及度量性畸变的指标,着重介绍了芳构化酶抑制假说与睾酮-硫络合物抑制假说等有关性畸变的机理,并结合作者个人体会提出以后要开展的研究内容. 相似文献
90.
双酚A(BPA)已被证实是一种类雌激素类物质。本研究根据BPA对水生生物毒性效应的特点,按照不同的毒性终点将BPA的毒性数据进行归类,采用物种敏感度分布法(species sensitivity distribution,SSD)推导了BPA对水生生物的预测无效应浓度(predicted no effect concentration,PNEC)。结果表明:以雌激素效应为暴露终点的急、慢性PNEC分别为25.11μg·L-1、1.075μg·L-1;而以所有数据的急、慢性毒性效应为暴露终点推导的PNEC值分别为355.7μg·L-1、7.549μg·L-1。BPA对水生生物的雌激素效应更为敏感,建议在推导BPA这类内分泌干扰物的PNEC值时,应依据其毒性终点分别推导,从而得到更加合理的基准值。研究成果以期为我国地表水环境质量标准的制修订提供数据支持。 相似文献