全文获取类型
收费全文 | 8167篇 |
免费 | 1164篇 |
国内免费 | 1653篇 |
专业分类
10984篇 |
出版年
2024年 | 44篇 |
2023年 | 247篇 |
2022年 | 274篇 |
2021年 | 402篇 |
2020年 | 488篇 |
2019年 | 725篇 |
2018年 | 629篇 |
2017年 | 536篇 |
2016年 | 507篇 |
2015年 | 461篇 |
2014年 | 499篇 |
2013年 | 736篇 |
2012年 | 360篇 |
2011年 | 491篇 |
2010年 | 405篇 |
2009年 | 485篇 |
2008年 | 515篇 |
2007年 | 502篇 |
2006年 | 422篇 |
2005年 | 324篇 |
2004年 | 353篇 |
2003年 | 258篇 |
2002年 | 217篇 |
2001年 | 199篇 |
2000年 | 147篇 |
1999年 | 125篇 |
1998年 | 128篇 |
1997年 | 72篇 |
1996年 | 82篇 |
1995年 | 71篇 |
1994年 | 58篇 |
1993年 | 66篇 |
1992年 | 56篇 |
1991年 | 27篇 |
1990年 | 14篇 |
1989年 | 6篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 10篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
951.
Fish commonly respond to stress, including stress from chemical exposures, with reduced growth. However, the relevance to wild populations of subtle and sometimes transitory growth reductions may not be obvious. At low-level, sustained exposures, Cu is one substance that commonly causes reduced growth but little mortality in laboratory toxicity tests with fish. To explore the relevance of growth reductions under laboratory conditions to wild populations, we (1) estimated growth effects of low-level Cu exposures to juvenile Chinook salmon (Oncorhynchus tshawytscha), (2) related growth effects to reduced survival in downriver Chinook salmon migrations, (3) estimated population demographics, (4) constructed a demographically structured matrix population model, and (5) projected the influence of Cu-reduced growth on population size, extinction risks, and recovery chances. Reduced juvenile growth from Cu in the range of chronic criteria concentrations was projected to cause disproportionate reductions in survival of migrating juveniles, with a 7.5% length reduction predicting about a 23% to 52% reduction in survival from a headwaters trap to the next census point located 640 km downstream. Projecting reduced juvenile growth out through six generations (~30 years) resulted in little increased extinction risk; however, population recovery times were delayed under scenarios where Cu-reduced growth was imposed. 相似文献
952.
Protein structure refinement is an important but unsolved problem; it must be solved if we are to predict biological function that is very sensitive to structural details. Specifically, critical assessment of techniques for protein structure prediction (CASP) shows that the accuracy of predictions in the comparative modeling category is often worse than that of the template on which the homology model is based. Here we describe a refinement protocol that is able to consistently refine submitted predictions for all categories at CASP7. The protocol uses direct energy minimization of the knowledge‐based potential of mean force that is based on the interaction statistics of 167 atom types (Summa and Levitt, Proc Natl Acad Sci USA 2007; 104:3177–3182). Our protocol is thus computationally very efficient; it only takes a few minutes of CPU time to run typical protein models (300 residues). We observe an average structural improvement of 1% in GDT_TS, for predictions that have low and medium homology to known PDB structures (Global Distance Test score or GDT_TS between 50 and 80%). We also observe a marked improvement in the stereochemistry of the models. The level of improvement varies amongst the various participants at CASP, but we see large improvements (>10% increase in GDT_TS) even for models predicted by the best performing groups at CASP7. In addition, our protocol consistently improved the best predicted models in the refinement category at CASP7 and CASP8. These improvements in structure and stereochemistry prove the usefulness of our computationally inexpensive, powerful and automatic refinement protocol. Proteins 2010. © 2010 Wiley‐Liss, Inc. 相似文献
953.
The new coarse graining model PRIMO/PRIMONA for proteins and nucleic acids is proposed. This model combines one to several heavy atoms into coarse‐grained sites that are chosen to allow an analytical, high‐resolution reconstruction of all‐atom models based on molecular bonding geometry constraints. The accuracy of proposed reconstruction method in terms of structure and energetics is tested and compared with other popular reconstruction methods for a variety of protein and nucleic acid test sets. Proteins 2010. © 2009 Wiley‐Liss, Inc. 相似文献
954.
955.
David A. Jacques Jill Trewhella 《Protein science : a publication of the Protein Society》2010,19(4):642-657
The last decade has seen a dramatic increase in the use of small‐angle scattering for the study of biological macromolecules in solution. The drive for more complete structural characterization of proteins and their interactions, coupled with the increasing availability of instrumentation and easy‐to‐use software for data analysis and interpretation, is expanding the utility of the technique beyond the domain of the biophysicist and into the realm of the protein scientist. However, the absence of publication standards and the ease with which 3D models can be calculated against the inherently 1D scattering data means that an understanding of sample quality, data quality, and modeling assumptions is essential to have confidence in the results. This review is intended to provide a road map through the small‐angle scattering experiment, while also providing a set of guidelines for the critical evaluation of scattering data. Examples of current best practice are given that also demonstrate the power of the technique to advance our understanding of protein structure and function. 相似文献
956.
Libusha Kelly Hisayo Fukushima Rachel Karchin Jason M Gow Leslie W Chinn Ursula Pieper Mark R Segal Deanna L Kroetz Andrej Sali 《Protein science : a publication of the Protein Society》2010,19(11):2110-2121
The human ATP‐binding cassette (ABC) transporter superfamily consists of 48 integral membrane proteins that couple the action of ATP binding and hydrolysis to the transport of diverse substrates across cellular membranes. Defects in 18 transporters have been implicated in human disease. In hundreds of cases, disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs). The functional impact of the majority of ABC transporter nsSNPs has yet to be experimentally characterized. Here, we combine experimental mutational studies with sequence and structural analysis to describe the impact of nsSNPs in human ABC transporters. First, the disease associations of 39 nsSNPs in 10 transporters were rationalized by identifying two conserved loops and a small α‐helical region that may be involved in interdomain communication necessary for transport of substrates. Second, an approach to discriminate between disease‐associated and neutral nsSNPs was developed and tailored to this superfamily. Finally, the functional impact of 40 unannotated nsSNPs in seven ABC transporters identified in 247 ethnically diverse individuals studied by the Pharmacogenetics of Membrane Transporters consortium was predicted. Three predictions were experimentally tested using human embryonic kidney epithelial (HEK) 293 cells stably transfected with the reference multidrug resistance transporter 4 and its variants to examine functional differences in transport of the antiviral drug, tenofovir. The experimental results confirmed two predictions. Our analysis provides a structural and evolutionary framework for rationalizing and predicting the functional effects of nsSNPs in this clinically important membrane transporter superfamily. 相似文献
957.
Gastone G. Celesia A. Townsend Peterson Julian C. Kerbis Peterhans Thomas P. Gnoske 《African Journal of Ecology》2010,48(1):58-71
Although many studies have documented aspects of lion ecology, they have generally focused on single sites, leaving broader-scaled factors unanalysed. We assessed range-wide effects of eight biotic and 26 abiotic variables on lion distribution and ecology, based on data compiled from published sources on lion population ecology in 27 protected areas in Africa. Lion pride size and composition were independent of lion density; lion density and home range size were inversely related; and lion density was positively related to rainfall, soil nutrients and annual mean temperature, with some interactive effects between rainfall and soil nutrients. Lion demography was associated most strongly with rainfall, temperature and landscape features. Herbivore biomass and lion density were correlated in univariate regression analyses. However, because herbivore biomass was also related to rainfall and temperature, hierarchical partitioning (HP) allowed us to evaluate independent effects of each variable on lion demography revealing that herbivore biomass had negligible independent contributions. HP indicated that climatic parameters explained 62% of overall variance in demographic parameters, whereas landscape features explained only 32%; climatic parameters were fairly balanced between effects of temperature (34%) and rainfall (28%). Prey (herbivore) biomass is important for lion survival, but its effects appear secondary to environmental factors. 相似文献
958.
959.
M.W. Marzke M.W. Tocheri B. Steinberg J.D. Femiani S.P. Reece R.L. Linscheid C.M. Orr R.F. Marzke 《American journal of physical anthropology》2010,141(1):38-51
Comparisons of joint surface curvature at the base of the thumb have long been made to discern differences among living and fossil primates in functional capabilities of the hand. However, the complex shape of this joint makes it difficult to quantify differences among taxa. The purpose of this study is to determine whether significant differences in curvature exist among selected catarrhine genera and to compare these genera with hominin1 fossils in trapeziometacarpal curvature. Two 3D approaches are used to quantify curvatures of the trapezial and metacarpal joint surfaces: (1) stereophotogrammetry with nonuniform rational B‐spline (NURBS) calculation of joint curvature to compare modern humans with captive chimpanzees and (2) laser scanning with a quadric‐based calculation of curvature to compare modern humans and wild‐caught Pan, Gorilla, Pongo, and Papio. Both approaches show that Homo has significantly lower curvature of the joint surfaces than does Pan. The second approach shows that Gorilla has significantly more curvature than modern humans, while Pongo overlaps with humans and African apes. The surfaces in Papio are more cylindrical and flatter than in Homo. Australopithecus afarensis resembles African apes more than modern humans in curvatures, whereas the Homo habilis trapezial metacarpal surface is flatter than in all genera except Papio. Neandertals fall at one end of the modern human range of variation, with smaller dorsovolar curvature. Modern human topography appears to be derived relative to great apes and Australopithecus and contributes to the distinctive human morphology that facilitates forceful precision and power gripping, fundamental to human manipulative activities. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc. 1 The term “hominin” refers to members of the tribe Hominini, which includes modern humans and fossil species that are related more closely to modern humans than to extant species of chimpanzees, Wood and Lonergan (2008). Hominins are in the family Hominidae with great apes. 相似文献
960.
Summary Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplotype effects for survival data. These estimating equations are simple to implement and avoid the use of the EM algorithm, which may be slow in the context of the semiparametric Cox model with incomplete covariate information. These estimating equations also lead to easily computable, direct estimators of standard errors, and thus overcome some of the difficulty in obtaining variance estimators based on the EM algorithm in this setting. We also develop an easily implemented goodness‐of‐fit procedure for Cox's regression model including haplotype effects. Finally, we apply the procedures presented in this article to investigate possible haplotype effects of the PAF‐receptor on cardiovascular events in patients with coronary artery disease, and compare our results to those based on the EM algorithm. 相似文献