首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   292篇
  免费   43篇
  2021年   5篇
  2017年   3篇
  2015年   8篇
  2014年   10篇
  2013年   10篇
  2012年   19篇
  2011年   23篇
  2010年   8篇
  2009年   7篇
  2008年   11篇
  2007年   19篇
  2006年   10篇
  2005年   20篇
  2004年   5篇
  2003年   9篇
  2002年   11篇
  2001年   6篇
  2000年   8篇
  1999年   9篇
  1998年   5篇
  1997年   3篇
  1996年   5篇
  1995年   2篇
  1994年   2篇
  1992年   6篇
  1991年   8篇
  1990年   5篇
  1989年   6篇
  1988年   11篇
  1987年   6篇
  1986年   6篇
  1985年   5篇
  1984年   3篇
  1983年   2篇
  1981年   4篇
  1979年   2篇
  1977年   5篇
  1976年   2篇
  1975年   2篇
  1974年   4篇
  1973年   6篇
  1972年   5篇
  1971年   2篇
  1970年   3篇
  1969年   3篇
  1968年   4篇
  1967年   2篇
  1966年   2篇
  1965年   2篇
  1961年   2篇
排序方式: 共有335条查询结果,搜索用时 15 毫秒
121.
122.
To understand controls over biodiversity, it is necessary to take a multi‐scale approach to understand how local and regional factors affect the community assembly processes that drive emergent patterns. This need is reflected in the growing use of the metacommunity concept to interpret multi‐scale measures of biodiversity, including metrics derived from diversity partitioning (e.g. α, β and γ diversity) and variation partitioning (e.g. spatial and environmental components of compositional turnover) techniques. However, studies have shown limited success using these metrics to characterize underlying community assembly dynamics. Here we demonstrate how a metacommunity simulation package (MCSim) can be used to evaluate when and how biodiversity metrics can be used to make inferences about metacommunity characteristics. We examined a wide range of parameter settings representing ecologically relevant scenarios. We used artificial neural networks (ANNs) to assess the sensitivity of diversity and variation partitioning metrics (calculated from simulation outcomes) to metacommunity parameter settings. In the scenarios examined in this study, the niche‐neutral gradient strongly influenced most biodiversity metrics, metacommunity size exhibited a marginal influence over some metrics, and dispersal dynamics only affected a subset of variation partitioning outcomes. Variation partitioning response curves along the niche‐neutral gradient were not monotonic; however, simulation outcomes suggest other biodiversity metrics (e.g. dissimilarity saturation) can be used in combination with variation partitioning metrics to make inferences about metacommunity properties. With the growing availability of archived ecological data, we expect future work will apply simulation‐based techniques to better understand links between biodiversity and the metacommunity characteristics that are presumed to control the underlying community assembly processes.  相似文献   
123.
Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) that participates in a broad range of cellular activities due to interaction with multiple binding partners. Tankyrase 1 recognizes a linear six-amino-acid degenerate motif and, hence, has hundreds of potential target proteins. Binding of partner proteins to tankyrase 1 usually results in their poly(ADP-ribosyl)ation (PARsylation) and can lead to ubiquitylation and proteasomal degradation. However, it is not known how tankyrase 1 PARP activity is regulated. Here we identify GDP-mannose 4,6-dehydratase (GMD) as a binding partner of tankyrase 1. GMD is a cytosolic protein required for the first step of fucose synthesis. We show that GMD is complexed to tankyrase 1 in the cytosol throughout interphase, but its association with tankyrase 1 is reduced upon entry into mitosis, when tankyrase 1 binds to its other partners TRF1 (at telomeres) and NuMA (at spindle poles). In contrast to other binding partners, GMD is not PARsylated by tankyrase 1. Indeed, we show that GMD inhibits tankyrase 1 PARP activity in vitro, dependent on the GMD tankyrase 1 binding motif. In vivo, depletion of GMD led to degradation of tankyrase 1, dependent on the catalytic PARP activity of tankyrase 1. We speculate that association of tankyrase 1 with GMD in the cytosol sequesters tankyrase 1 in an inactive stable form that can be tapped by other target proteins as needed.  相似文献   
124.
ABSTRACT: BACKGROUND: The mechanisms of the antinociceptive activity of () epicatechin (EPI), a compound isolated from the hydroalcoholic fraction of Combreum leprosum Mart & Eicher. METHODS: were assessed in the model of chemical nociception induced by glutamate (20 mumol/paw). To evaluate the mechanisms involved, the animals , male Swiss mice (25-30 g), received EPI (50 mg/kg p.o.) after pretreatment with naloxone (2 mg/kg s.c. opioid antagonist), glibenclamide (2 mg/kg s.c. antagonist K + channels sensitive to ATP), ketanserin (0.3 mg/kg s.c. antagonist of receptor 5-HT2A), yoimbine (0.15 mg/kg s.c. alpha2 adrenergic receptor antagonist), pindolol (1 mg/kg s.c. 5-HT1a/1b receptor antagonist), atropine (0.1 mg/kg s.c. muscarinic antagonist) and caffeine (3 mg/kg s.c. adenosine receptor antagonist), ondansetron (0.5 mg/kg s.c. for 5-HT3 receptor) and L-arginine (600 mg/kg i.p.). RESULTS: The antinociceptive effect of EPI was reversed by pretreatment with naloxone and glibenclamide, ketanserin, yoimbine, atropine and pindolol, which demonstrates the involvement of opioid receptors and potassium channels sensitive to ATP, the serotoninergic (receptor 5HT1A and 5HT2A), adrenergic (receptor alpha 2) and cholinergic (muscarinic receptor) systems in the activities that were observed. The effects of EPI, however, were not reversed by pretreatment with caffeine, L-arginine or ondansetron, which shows that there is no involvement of 5HT3 receptors or the purinergic and nitrergic systems in the antinociceptive effect of EPI. In the Open Field and Rotarod test, EPI had no significant effect, which shows that there was no central nervous system depressant or muscle relaxant effect on the results. CONCLUSIONS: This study demonstrates that the antinociceptive activity of EPI in the glutamate model involves the participation of the opioid system, serotonin, adrenergic and cholinergic.  相似文献   
125.
R J Sokol 《Acta anatomica》1988,133(2):140-142
Morphometric methods were used to study the nucleolar ultrastructure during the development of human blood monocytes into macrophages in suspension culture. Nucleolar volume (Vn), surface area (Sn), volume fraction within the nucleus (VVn), surface-to-volume ratio [(S/V)n] and number of nucleolar profiles per section were measured in 20 healthy adults over a 6-day period, and the results examined using multivariate and univariate analyses of variance. Highly significant increases in Vn, Sn and VVn occurred, with no significant change in the number of nucleolar profiles per section; (S/V)n decreased during culture; no significant differences were found between male and female subjects. These nucleolar changes would be consistent with an increased protein synthesis during macrophage development. The results provide quantitative data against which changes in nucleolar morphology during macrophage development in disease states may be assessed.  相似文献   
126.
The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath, the reversal potential of whole-cell currents was governed by the prevailing Cl- equilibrium potential and could be fitted by the Goldman-Hodgkin-Katz equation with similar permeabilities for uninfected and beta-Gal cells. In the frequency range 0.12 < f < 300 Hz, the power density spectrum of whole-cell Cl- currents could be fitted by three Lorentzians. Independent of membrane potential, >50% of the total variance of whole-cell current fluctuations was accounted for by the low frequency Lorentzian (fc = 0.40 +/- 0.03 Hz, n = 6). Single-Cl- channels showed complex gating kinetics with long lasting (seconds) openings interrupted by similar long closures. In the open state, channels exhibited fast burst-like closures. Since the patches normally contained more than a single channel, it was not possible to measure open and closed dwell-time distributions for comparing single-Cl- channel activity with the kinetic features of whole-cell currents. However, the power density spectrum of Cl- currents of cell-attached and excised outside-out patches contained both high and low frequency Lorentzian components, with the corner frequency of the slow component (fc = 0.40 +/- 0.02 Hz, n = 4) similar to that of whole-cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150/150) of approximately 3.5 pS and approximately 35 pS, respectively. All states reversed near the same membrane potential, and they exhibited similar halide ion selectivity, P1 > PCl approximately PBr. Accordingly, Cl- current amplitudes larger than current flow through the smallest channel unit resolved seem to result from simultaneous open/shut events of two or more channel units.  相似文献   
127.
Injected Wnt RNA induces a complete body axis in Xenopus embryos.   总被引:20,自引:0,他引:20  
S Sokol  J L Christian  R T Moon  D A Melton 《Cell》1991,67(4):741-752
Studies in Xenopus have shown that growth factors of the TGF beta and Wnt oncogene families can mimic aspects of dorsal axis formation. Here we directly compare the inductive properties of two Wnt proteins by injecting synthetic mRNA into developing embryos. The results show that Wnt-1 and Xwnt-8 can induce a new and complete dorsal axis and can rescue the development of axis-deficient, UV-irradiated embryos. In contrast, activin mRNA injection induces only a partial dorsal axis that lacks anterior structures. These studies demonstrate that the mechanism of Wnt-induced axis duplication results from the creation of an independent Spemann organizer. The relationship between the properties of the endogenous dorsal inducer and the effects of Wnts and activins is discussed.  相似文献   
128.
Iron affects yields of toxin A, alkaline protease, elastase, pyochelin, and pyoverdin in Pseudomonas aeruginosa. Mutants of P. aeruginosa PAO1 resistant to the effect of iron on toxin (toxC) or elastase (elaC) yields were isolated. Two types of mutants were isolated: iron transport and iron regulatory mutants. The toxC regulatory mutants produced toxin A in medium containing iron; however, yields of elastase and alkaline protease remained sensitive to regulation by iron. The elaC regulatory mutants were resistant to the effect of iron on elastase yields, but toxin A and alkaline protease yields were decreased by iron, analogous to the parent strain. These data suggest that toxin A, elastase, and alkaline protease yields can be independently regulated by iron.  相似文献   
129.
130.
With the increasing incidence of coronary heart disease (CHD) and the subsequent interest in factors which contribute to its development, the idea of a coronary-prone (Type A) behavior pattern has attracted much attention in recent years. In this paper, research on the coronary-prone behavior pattern is reviewed. Type A behavior is found to be fairly accurate in predicting the likelihood and severity of CHD, at least in large groups of people. Problems in measuring and in more clearly defining the components of Type A behavior are discussed. Future investigations are urged, focusing on how the behavior pattern develops and on strategies for intervention.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号