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   3453篇
  免费   346篇
  国内免费   3篇
  3802篇
  2022年   22篇
  2021年   44篇
  2020年   34篇
  2019年   30篇
  2018年   58篇
  2017年   56篇
  2016年   79篇
  2015年   139篇
  2014年   168篇
  2013年   171篇
  2012年   231篇
  2011年   215篇
  2010年   145篇
  2009年   136篇
  2008年   191篇
  2007年   193篇
  2006年   217篇
  2005年   184篇
  2004年   170篇
  2003年   168篇
  2002年   174篇
  2001年   71篇
  2000年   44篇
  1999年   48篇
  1998年   46篇
  1997年   35篇
  1996年   42篇
  1995年   42篇
  1994年   44篇
  1993年   29篇
  1992年   62篇
  1991年   45篇
  1990年   39篇
  1989年   41篇
  1988年   32篇
  1987年   22篇
  1986年   25篇
  1985年   31篇
  1984年   19篇
  1983年   21篇
  1982年   21篇
  1980年   13篇
  1979年   17篇
  1978年   14篇
  1977年   13篇
  1976年   14篇
  1974年   14篇
  1973年   11篇
  1972年   11篇
  1971年   12篇
排序方式: 共有3802条查询结果,搜索用时 15 毫秒
91.
Over the last decades, political, economic and environmental pressures have encouraged changes from swidden to more intensive agricultural practices, resulting in the hypothesis that swidden cultivation systems are disappearing. In Calakmul, southeastern Mexico, communities decreased the area under milpa, the traditional maize swidden system, but a collapse did not occur. To document and explain the persistence of swidden we employ a variety of data: (1) 59 standardized household surveys from 2003 and 2010 in five villages, (2) in-depth interviews in one village, and (3) coupled human–environmental timelines in this same village. Droughts, hurricanes, and remittances were important drivers of decreases in milpa cultivation. Market crop profitability and conservation programs were also reported to affect the area under milpa. Off-farm employment and governmental transfers have tended to stabilize household economies and decrease dependency on agricultural production, but have also allowed households to maintain their milpas for subsistence and cultural reproduction. Findings in Calakmul point to the need to consider swidden as an evolving and active response to changing policy, economic, and environmental conditions.  相似文献   
92.
93.
94.
Recruitment of the growth factor receptor-bound protein 2 (Grb2) by the plasma membrane-associated adapter protein downstream of kinase 3 (Dok-3) attenuates signals transduced by the B cell antigen receptor (BCR). Here we describe molecular details of Dok-3/Grb2 signal integration and function, showing that the Lyn-dependent activation of the BCR transducer kinase Syk is attenuated by Dok-3/Grb2 in a site-specific manner. This process is associated with the SH3 domain-dependent translocation of Dok-3/Grb2 complexes into BCR microsignalosomes and augmented phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5′ phosphatase. Hence, our findings imply that Dok-3/Grb2 modulates the balance between activatory and inhibitory Lyn functions with the aim to adjust BCR signaling efficiency.  相似文献   
95.
Saccharomyces cerevisiae, as well as other eukaryotes, preserves fatty acids and sterols in a biologically inert form, as triacylglycerols and steryl esters. The major triacylglycerol lipases of the yeast S. cerevisiae identified so far are Tgl3p, Tgl4p, and Tgl5p (Athenstaedt, K., and Daum, G. (2003) YMR313c/TGL3 encodes a novel triacylglycerol lipase located in lipid particles of Saccharomyces cerevisiae. J. Biol. Chem. 278, 23317–23323; Athenstaedt, K., and Daum, G. (2005) Tgl4p and Tgl5p, two triacylglycerol lipases of the yeast Saccharomyces cerevisiae, are localized to lipid particles. J. Biol. Chem. 280, 37301–37309). We observed that upon cultivation on oleic acid, triacylglycerol mobilization did not come to a halt in a yeast strain deficient in all currently known triacylglycerol lipases, indicating the presence of additional not yet characterized lipases/esterases. Functional proteome analysis using lipase and esterase inhibitors revealed a subset of candidate genes for yet unknown hydrolytic enzymes on peroxisomes and lipid droplets. Based on the conserved GXSXG lipase motif, putative functions, and subcellular localizations, a selected number of candidates were characterized by enzyme assays in vitro, gene expression analysis, non-polar lipid analysis, and in vivo triacylglycerol mobilization assays. These investigations led to the identification of Ayr1p as a novel triacylglycerol lipase of yeast lipid droplets and confirmed the hydrolytic potential of the peroxisomal Lpx1p in vivo. Based on these results, we discuss a possible link between lipid storage, lipid mobilization, and peroxisomal utilization of fatty acids as a carbon source.  相似文献   
96.
Sinorhizobium meliloti of the order Rhizobiales is a symbiotic nitrogen-fixing bacterium nodulating plants of the genera Medicago, Trigonella and Melilotus and hence is of great agricultural importance. In its free-living state it is motile and capable of modulating its movement patterns in response to chemical attractants. Here, the draft genome consisting of a circular chromosome, the megaplasmids pSymA and pSymB and three accessory plasmids of Sinorhizobium meliloti RU11/001, a model organism for flagellum structure, motility and chemotaxis, is reported.  相似文献   
97.
Several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases as well as nonneuropathic diseases such as type II diabetes and atrial amyloidosis are associated with aggregation of amyloid polypeptides into fibrillar structures, or plaques. In this study, we use molecular dynamics simulations to test the stability and orientation of membrane-embedded aggregates of the human islet amyloid polypeptide (hIAPP) implicated in type II diabetes. We find that in both monolayers and bilayers of dipalmitoylphosphatidylglycerol (DPPG) hIAPP trimers and tetramers remain inside the membranes and preserve their β-sheet secondary structure. Lipid bilayer-inserted hIAPP trimers and tetramers orient inside DPPG at 60° relative to the membrane/water interface and lead to water permeation and Na+ intrusion, consistent with ion-toxicity in islet β-cells. In particular, hIAPP trimers form a water-filled β-sandwich that induce water permeability comparable with channel-forming proteins, such as aquaporins and gramicidin-A. The predicted disruptive orientation is consistent with the amphiphilic properties of the hIAPP aggregates and could be probed by chiral sum frequency generation (SFG) spectroscopy, as predicted by the simulated SFG spectra.  相似文献   
98.
Several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases as well as nonneuropathic diseases such as type II diabetes and atrial amyloidosis are associated with aggregation of amyloid polypeptides into fibrillar structures, or plaques. In this study, we use molecular dynamics simulations to test the stability and orientation of membrane-embedded aggregates of the human islet amyloid polypeptide (hIAPP) implicated in type II diabetes. We find that in both monolayers and bilayers of dipalmitoylphosphatidylglycerol (DPPG) hIAPP trimers and tetramers remain inside the membranes and preserve their β-sheet secondary structure. Lipid bilayer-inserted hIAPP trimers and tetramers orient inside DPPG at 60° relative to the membrane/water interface and lead to water permeation and Na+ intrusion, consistent with ion-toxicity in islet β-cells. In particular, hIAPP trimers form a water-filled β-sandwich that induce water permeability comparable with channel-forming proteins, such as aquaporins and gramicidin-A. The predicted disruptive orientation is consistent with the amphiphilic properties of the hIAPP aggregates and could be probed by chiral sum frequency generation (SFG) spectroscopy, as predicted by the simulated SFG spectra.  相似文献   
99.
This study aimed at visualization of cyclooxygenase-2 (COX-2) protein expression in melanoma cells by confocal laser induced cryofluorescence microscopy using 4-(3-(4-methoxyphenyl)-1H-indol-2-yl)benzene-sulfonamide (C1) representative for a novel class of autofluorescent 2,3-diarylsubstituted indole-based selective COX-2 inhibitors.COX-2 expression was measured in human melanoma cell lines A2058 and MelJuso by immunocytochemistry and immunoblotting. Cellular uptake experiments using varying C1 concentrations down to 0.1 nM (with/without molar excess of celecoxib as control) were performed at 37 °C. Cryofluorescence microscopy was conducted at 20 K.COX-2 protein expression was successfully visualized by C1 in A2058 cells. COX-2-negative MelJuso cells showed no specific accumulation of C1. Control experiments using celecoxib and, additionally, implemented fluorescence spectroscopy confirmed specificity of both cellular uptake and intracellular association of C1.Cryofluorescence microscopy in combination with spectroscopy allowed for visualization of COX-2 protein expression in melanoma cells in vitro using a selective COX-2 inhibitor at very low concentrations.  相似文献   
100.
Firing-rate models provide a practical tool for studying signal processing in the early visual system, permitting more thorough mathematical analysis than spike-based models. We show here that essential response properties of relay cells in the lateral geniculate nucleus (LGN) can be captured by surprisingly simple firing-rate models consisting of a low-pass filter and a nonlinear activation function. The starting point for our analysis are two spiking neuron models based on experimental data: a spike-response model fitted to data from macaque (Carandini et al. J. Vis., 20(14), 1–2011, 2007), and a model with conductance-based synapses and afterhyperpolarizing currents fitted to data from cat (Casti et al. J. Comput. Neurosci., 24(2), 235–252, 2008). We obtained the nonlinear activation function by stimulating the model neurons with stationary stochastic spike trains, while we characterized the linear filter by fitting a low-pass filter to responses to sinusoidally modulated stochastic spike trains. To account for the non-Poisson nature of retinal spike trains, we performed all analyses with spike trains with higher-order gamma statistics in addition to Poissonian spike trains. Interestingly, the properties of the low-pass filter depend only on the average input rate, but not on the modulation depth of sinusoidally modulated input. Thus, the response properties of our model are fully specified by just three parameters (low-frequency gain, cutoff frequency, and delay) for a given mean input rate and input regularity. This simple firing-rate model reproduces the response of spiking neurons to a step in input rate very well for Poissonian as well as for non-Poissonian input. We also found that the cutoff frequencies, and thus the filter time constants, of the rate-based model are unrelated to the membrane time constants of the underlying spiking models, in agreement with similar observations for simpler models.  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