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Rab GTPases regulate membrane traffic between the cellular compartments of eukaryotic cells. Rab3 is associated with secretory vesicles of neuronal and endocrine cells and controls the Ca(2+)-triggered release of neurotransmitters and hormones. To clarify the mode of action of Rab3 we generated mutants of the GTPase that do not interact efficiently with its putative effectors Rabphilin and RIM. Surprisingly, these mutants transfected in PC12 cells were still capable of inhibiting Ca(2+)-evoked secretion. Rab3 was shown previously to bind to calmodulin in a Ca(2+)-dependent manner. By replacing two arginines conserved between Rab3 isoforms, we generated a mutant with a reduced affinity for calmodulin. This mutant retained the capacity to interact with the Rab3 regulatory proteins, Rabphilin, RIM, Mss4 and RabGDI, and was correctly targeted to dense-core secretory granules. However, replacement of the two arginines abolished the ability of the GTP-bound form of Rab3 to inhibit exocytosis of catecholamine- and insulin-secreting cells. We propose that a Rab3-calmodulin complex generated by elevated Ca(2+) concentrations mediated at least some of the effects of the GTPase and limited the number of exocytotic events that occurred in response to secretory stimuli.  相似文献
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Costing eradications of alien mammals from islands   总被引:2,自引:0,他引:2  
The ability to estimate costs of alien species eradications is essential for a rigorous assessment of priorities for island restoration. Using a global data file from 41 islands, mostly gleaned from the 'grey' literature, we show that the cost of vertebrate eradications can be satisfactorily predicted if island area and species to be eradicated are known. About 72% of the variation in cost can be explained by island area, whereas, for a given area, rodent eradications are 1.7–3.0 times more expensive than ungulate eradications. Costs per hectare decrease with island size. Restricting the analysis to roughly half the data set, the relatively homogeneous half concerned with New Zealand islands, we identify two further influences on cost: date of eradication and distance to the main airport (an indicator of remoteness). For a given area, costs have declined over time but increase with island remoteness. This information therefore provides conservation planners with a robust, if preliminary, estimate of the cost of any proposed eradication programme.  相似文献
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Thiamine (Vitamin B1) is a co-factor for enzymes key in bridging aerobic and anaerobic metabolism. One such enzyme, transketolase, catalyzes two of three reactions for entry into the pentose-phosphate pathway, a major source of chemical reducing power. Thus, thiamine deprivation (TD) is considered a classic model of systemic oxidative stress and is linked with degenerative diseases. TD in mice and rats produces neurodegeneration with Alzheimer's disease characteristics. Age-related disease of the lens, commonly cataract, is also linked with thiamine and oxidative stress. To test the effects of TD on mice, we used a previously defined protocol involving a thiamine free diet and a thiamine antagonist. After 12 days, lens fiber cell degeneration was observed primarily along the lens posterior beneath the intact capsule. These regions exhibited a localized increased expression of Alzheimer precursor protein, Abeta peptides, and presenilin 1. These data indicate that TD in mice produces fiber cell degeneration and suggest common mechanisms for TD-induced lens fiber and neuronal cell degeneration.  相似文献
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The relationship between the concentrations of total and apparent free testosterone in the plasma and the levels of testosterone (T), dihydrotestosterone (DHT) and 5 alpha-androstan-3-alpha, 17 beta-diol (DIOL) in 13 benign hypertrophic and 6 carcinomatous prostates was studied. The androgen concentration within both types of glands was nearly 4-fold that in the blood but bore no direct relationship to the blood level. About 75% of the androgen in the tissue was DHT. The most striking finding was that, in spite of a 25.5% less concentrated pool of apparent free testosterone in the blood, the level of T and its metabolites in the cancer tissue was 29% above that in the samples of benign hypertrophic prostate.  相似文献
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Earlier work had shown that the lactogen, LTH and HPL, foster testosterone binding by the prostate. This study was undertaken to see if prostaglandin F2alpha would oppose the effect of the lactogen on the prostate as it does the luteotrophic action of the hormone on the corpus luteum. When it was found instead that the PGF increases steroid binding and that its interaction with lactogen was neither antagonistic nor additive, attention was directed to further characterization of prostaglandin's effect. A dosage/response study of F2alpha alone showed that concentrations of 4 ng/ml and 40 ng/ml increased binding but that 400 ng/ml did not. Glands with stromal hyperplasia and/or inflammation were not responsive than those with epithelial hyperplasia. Assays of water extracts of the tissue revealed concentrations of about 340 ng of F2alpha per gram fresh weight and that the concentration varied inversely as the beta-glucuronidase activity. If the enzyme level is considered an index of the epithelial cell density within the specimen, the inverse relationship suggest a non-epithelial (stromal) site of prostaglandin concentration.  相似文献
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A capacity to predict the effects of fire on biota is critical for conservation in fire‐prone regions as it assists managers to anticipate the outcomes of different approaches to fire management. The task is complicated because species’ responses to fire can vary geographically. This poses challenges, both for conceptual understanding of post‐fire succession and fire management. We examine two hypotheses for why species may display geographically varying responses to fire. 1) Species’ post‐fire responses are driven by vegetation structure, but vegetation – fire relationships vary spatially (the ‘dynamic vegetation’ hypothesis). 2) Regional variation in ecological conditions leads species to select different post‐fire ages as habitat (the ‘dynamic habitat’ hypothesis). Our case study uses data on lizards at 280 sites in a ∼ 100 000 km2 region of south‐eastern Australia. We compared the predictive capacity of models based on 1) habitat associations, with models based on 2) fire history and vegetation type, and 3) fire history alone, for four species of lizards. Habitat association models generally out‐performed fire history models in terms of predictive capacity. For two species, habitat association models provided good discrimination capacity even though the species showed geographically varying post‐fire responses. Our results support the dynamic vegetation hypothesis, that spatial variation in relationships between fire and vegetation structure results in regional variation in fauna–fire relationships. These observations explain how the widely recognised ‘habitat accommodation’ model of animal succession can be conceptually accurate yet predictively weak.  相似文献
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