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511.
Online searching in publically available patent files opens up interesting possibilities to provide a rapid response to critical questions. A computerized analysis of all patents of leading German pharmaceutical companies over the last decade in important indication areas is described. Supported by subsequent manual processing of individual patents it is shown that duplicate experiments on animals practically never occur.  相似文献   
512.
The excellent technical assistance of H. Führer and I. Leib is appreciated. Part of the work was supported by the Bundesministerium für Forschung und Technologie, the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and from the Leitz and Hoechst companies. This paper is part of the M. D. thesis of Ch.L.  相似文献   
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Recent years have shown a rise in mean global temperatures and a shift in the geographical distribution of ectothermic animals. For a cause and effect analysis the present paper discusses those physiological processes limiting thermal tolerance. The lower heat tolerance in metazoa compared with unicellular eukaryotes and bacteria suggests that a complex systemic rather than molecular process is limiting in metazoa. Whole-animal aerobic scope appears as the first process limited at low and high temperatures, linked to the progressively insufficient capacity of circulation and ventilation. Oxygen levels in body fluids may decrease, reflecting excessive oxygen demand at high temperatures or insufficient aerobic capacity of mitochondria at low temperatures. Aerobic scope falls at temperatures beyond the thermal optimum and vanishes at low or high critical temperatures when transition to an anaerobic mitochondrial metabolism occurs. The adjustment of mitochondrial densities on top of parallel molecular or membrane adjustments appears crucial for maintaining aerobic scope and for shifting thermal tolerance. In conclusion, the capacity of oxygen delivery matches full aerobic scope only within the thermal optimum. At temperatures outside this range, only time-limited survival is supported by residual aerobic scope, then anaerobic metabolism and finally molecular protection by heat shock proteins and antioxidative defence. In a cause and effect hierarchy, the progressive increase in oxygen limitation at extreme temperatures may even enhance oxidative and denaturation stress. As a corollary, capacity limitations at a complex level of organisation, the oxygen delivery system, define thermal tolerance limits before molecular functions become disturbed.  相似文献   
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 This study investigated the influence of cat urine odour in suppressing development and fertility in Campbell's hamster males. Exposure to this odour from postnatal day 11 until day 45 (sexual maturation) resulted in reduced sex organ weights, reduced testosterone levels and in an increase in abnormalities of the synaptonemal complex in both sex chromosomes and autosomes. Subsequent breeding experiments revealed a significant decrease in litter size. All these data indicate a severe effect of predator odour on the breeding success of potential prey species. It is assumed that these effects are caused by the sulphurous compounds in the urine; however, the underlying mechanisms are not yet known. Received: 31 January 2000 / Accepted in revised form: 6 June 2000  相似文献   
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Until recently, scientists believed that the chemical elements were synthesized only in stars. The discovery of the Oklo phenomenon in the Republic of Gabon in 1972 has revealed, however, that a nuclear “fire” had existed on the earth and largescale transmutations of the elements were occurring on our planet 1.7·109 years ago. The formation of natural (or Pre-Fermi) reactors is closely related to the appearance of life on our planet earth. The Pre-Fermi reactors were probably never formed until about 2·109 years ago, when oxygen was injected into the earth's atmosphere by a new generation of living organisms carrying out photosynthesis.  相似文献   
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