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   570篇
  免费   49篇
  国内免费   1篇
  620篇
  2023年   7篇
  2022年   10篇
  2021年   24篇
  2020年   20篇
  2019年   13篇
  2018年   14篇
  2017年   14篇
  2016年   25篇
  2015年   37篇
  2014年   47篇
  2013年   39篇
  2012年   50篇
  2011年   52篇
  2010年   28篇
  2009年   20篇
  2008年   32篇
  2007年   36篇
  2006年   32篇
  2005年   30篇
  2004年   23篇
  2003年   24篇
  2002年   19篇
  2001年   2篇
  2000年   6篇
  1999年   1篇
  1998年   3篇
  1997年   3篇
  1996年   2篇
  1995年   4篇
  1994年   2篇
  1990年   1篇
排序方式: 共有620条查询结果,搜索用时 0 毫秒
81.
Odd-nosed monkeys represent one of the two major groups of Asian colobines. Our knowledge about this primate group is still limited as it is highlighted by the recent discovery of a new species in Northern Myanmar. Although a common origin of the group is now widely accepted, the phylogenetic relationships among its genera and species, and the biogeographic processes leading to their current distribution are largely unknown. To address these issues, we have analyzed complete mitochondrial genomes and 12 nuclear loci, including one X chromosomal, six Y chromosomal and five autosomal loci, from all ten odd-nosed monkey species. The gene tree topologies and divergence age estimates derived from different markers were highly similar, but differed in placing various species or haplogroups within the genera Rhinopithecus and Pygathrix. Based on our data, Rhinopithecus represent the most basal lineage, and Nasalis and Simias form closely related sister taxa, suggesting a Northern origin of odd-nosed monkeys and a later invasion into Indochina and Sundaland. According to our divergence age estimates, the lineages leading to the genera Rhinopithecus, Pygathrix and Nasalis+Simias originated in the late Miocene, while differentiation events within these genera and also the split between Nasalis and Simias occurred in the Pleistocene. Observed gene tree discordances between mitochondrial and nuclear datasets, and paraphylies in the mitochondrial dataset for some species of the genera Rhinopithecus and Pygathrix suggest secondary gene flow after the taxa initially diverged. Most likely such events were triggered by dramatic changes in geology and climate within the region. Overall, our study provides the most comprehensive view on odd-nosed monkey evolution and emphasizes that data from differentially inherited markers are crucial to better understand evolutionary relationships and to trace secondary gene flow.  相似文献   
82.
Accumulation of aberrant proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response pathway that helps the cell to survive under these stress conditions. Herp is a mammalian ubiquitin domain protein, which is strongly induced by the unfolded protein response. It is involved in ER-associated protein degradation (ERAD) and interacts directly with the ubiquitin ligase Hrd1, which is found in high molecular mass complexes of the ER membrane. Here we present the first evidence that Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like (UBL) domain-dependent manner. We found that upon exposure of cells to ER stress, elevation of Herp steady state levels is accompanied by an enhanced association of Herp with pre-existing Hrd1. Hrd1-associated Herp is rapidly degraded and substituted by de novo synthesized Herp, suggesting a continuous turnover of the protein at Hrd1 complexes. Further analysis revealed the presence of multiple Hrd1 copies in a single complex enabling binding of a variable number of Herp molecules. Efficient ubiquitylation of the Hrd1-specific ERAD substrate α1-antitrypsin null Hong Kong (NHK) required the presence of the Herp UBL domain, which was also necessary for NHK degradation. In summary, we propose that binding of Herp to Hrd1-containing ERAD complexes positively regulates the ubiquitylation activity of these complexes, thus permitting survival of the cell during ER stress.  相似文献   
83.
Woody vegetation in global tropical drylands is of significant importance for both the interannual variability of the carbon cycle and local livelihoods. Satellite observations over the past decades provide a unique way to assess the vegetation long‐term dynamics across biomes worldwide. Yet, the actual changes in the woody vegetation are always hidden by interannual fluctuations of the leaf density, because the most widely used remote sensing data are primarily related to the photosynthetically active vegetation components. Here, we quantify the temporal trends of the nonphotosynthetic woody components (i.e., stems and branches) in global tropical drylands during 2000–2012 using the vegetation optical depth (VOD), retrieved from passive microwave observations. This is achieved by a novel method focusing on the dry season period to minimize the influence of herbaceous vegetation and using MODerate resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) data to remove the interannual fluctuations of the woody leaf component. We revealed significant trends (< 0.05) in the woody component (VODwood) in 35% of the areas characterized by a nonsignificant trend in the leaf component (VODleaf modeled from NDVI), indicating pronounced gradual growth/decline in woody vegetation not captured by traditional assessments. The method is validated using a unique record of ground measurements from the semiarid Sahel and shows a strong agreement between changes in VODwood and changes in ground observed woody cover (r2 = 0.78). Reliability of the obtained woody component trends is also supported by a review of relevant literatures for eight hot spot regions of change. The proposed approach is expected to contribute to an improved assessment of, for example, changes in dryland carbon pools.  相似文献   
84.
The EUROCarbDB project is a design study for a technical framework, which provides sophisticated, freely accessible, open-source informatics tools and databases to support glycobiology and glycomic research. EUROCarbDB is a relational database containing glycan structures, their biological context and, when available, primary and interpreted analytical data from high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance experiments. Database content can be accessed via a web-based user interface. The database is complemented by a suite of glycoinformatics tools, specifically designed to assist the elucidation and submission of glycan structure and experimental data when used in conjunction with contemporary carbohydrate research workflows. All software tools and source code are licensed under the terms of the Lesser General Public License, and publicly contributed structures and data are freely accessible. The public test version of the web interface to the EUROCarbDB can be found at http://www.ebi.ac.uk/eurocarb.  相似文献   
85.
86.
The relationship between body mass (M) and size class abundance (N) depicts patterns of community structure and energy flow through food webs. While the general assumption is that M and N scale linearly (on log–log axes), nonlinearity is regularly observed in natural systems, and is theorized to be driven by nonlinear scaling of trophic level (TL) with M resulting in the rapid transfer of energy to consumers in certain size classes. We tested this hypothesis with data from 31 stream food webs. We predicted that allochthonous subsidies higher in the web results in nonlinear M–TL relationships and systematic abundance peaks in macroinvertebrate and fish size classes (latter containing salmonids), that exploit terrestrial plant material and terrestrial invertebrates, respectively. Indeed, both M–N and M–TL significantly deviated from linear relationships and the observed curvature in M–TL scaling was inversely related to that observed in M–N relationships. Systemic peaks in M–N, and troughs in M–TL occurred in size classes dominated by generalist invertebrates, and brown trout. Our study reveals how allochthonous resources entering high in the web systematically shape community size structure and demonstrates the relevance of a generalized metabolic scaling model for understanding patterns of energy transfer in energetically ‘open’ food webs.  相似文献   
87.
Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics‐inspired motion planning procedure called dCC‐RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non‐native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eight proteins determined in two conformations separated by, on average, 7.5 Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. We then applied dCC‐RRT to examine how collective, small‐scale motions of four side‐chains in the active site of cyclophilin A propagate through the protein. dCC‐RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non‐canonical capsid binding site 25 Å away, rationalizing NMR and multi‐temperature crystallography experiments. In all, dCC‐RRT can reveal detailed, all‐atom molecular mechanisms for small and large amplitude motions. Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/ .  相似文献   
88.
Cross‐border studies offer unique situations to study the impact of different land‐use regimes on ecosystems. Along the Angolan and Namibian border formed by the Okavango River, the environmental conditions and traditional land‐use practises are the same on either side of the river. However, decades of civil war in Angola led to a stagnant development while political stability in Namibia fostered a recent socio‐economic transformation. We investigated the impact of spatially diffuse land use on plant diversity of the dry tropical woodlands covering the vast, sandy hinterlands of the river. As accessibility is the major factor governing land use, we used distance to road as a proxy for land‐use intensity. Based on 58 vegetation plots sized 20 m × 50 m, we showed that species richness increased with distance to road in Angola while in Namibia it remained constant on a lower level. Evenness showed an inverse pattern to species richness and Shannon diversity index showed no response. Analysing diversity patterns according to life forms revealed that these patterns are primarily driven by woody species. The study showed that spatially diffuse land use has a measurable effect on plant diversity and illustrates that roads act as vectors of change.  相似文献   
89.
Current models of codon substitution are formulated at the levels of nucleotide substitution and do not explicitly consider the separate effects of mutation and selection. They are thus incapable of inferring whether mutation or selection is responsible for evolution at silent sites. Here we implement a few population genetics models of codon substitution that explicitly consider mutation bias and natural selection at the DNA level. Selection on codon usage is modeled by introducing codon-fitness parameters, which together with mutation-bias parameters, predict optimal codon frequencies for the gene. The selective pressure may be for translational efficiency and accuracy or for fine-tuning translational kinetics to produce correct protein folding. We apply the models to compare mitochondrial and nuclear genes from several mammalian species. Model assumptions concerning codon usage are found to affect the estimation of sequence distances (such as the synonymous rate d(S), the nonsynonymous rate d(N), and the rate at the 4-fold degenerate sites d(4)), as found in previous studies, but the new models produced very similar estimates to some old ones. We also develop a likelihood ratio test to examine the null hypothesis that codon usage is due to mutation bias alone, not influenced by natural selection. Application of the test to the mammalian data led to rejection of the null hypothesis in most genes, suggesting that natural selection may be a driving force in the evolution of synonymous codon usage in mammals. Estimates of selection coefficients nevertheless suggest that selection on codon usage is weak and most mutations are nearly neutral. The sensitivity of the analysis on the assumed mutation model is discussed.  相似文献   
90.
The 20S Proteasome as an Assembly Platform for the 19S Regulatory Complex   总被引:1,自引:0,他引:1  
26S proteasomes consist of cylindrical 20S proteasomes with 19S regulatory complexes attached to the ends. Treatment with high concentrations of salt causes the regulatory complexes to separate into two sub-complexes, the base, which is in contact with the 20S proteasome, and the lid, which is the distal part of the 19S complex. Here, we describe two assembly intermediates of the human regulatory complex. One is a dimer of the two ATPase subunits, Rpt3 and Rpt6. The other is a complex of nascent Rpn2, Rpn10, Rpn11, Rpn13, and Txnl1, attached to preexisting 20S proteasomes. This early assembly complex does not yet contain Rpn1 or any of the ATPase subunits of the base. Thus, assembly of 19S regulatory complexes takes place on preexisting 20S proteasomes, and part of the lid is assembled before the base.  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