全文获取类型
收费全文 | 585篇 |
免费 | 52篇 |
国内免费 | 1篇 |
专业分类
638篇 |
出版年
2023年 | 7篇 |
2022年 | 10篇 |
2021年 | 24篇 |
2020年 | 20篇 |
2019年 | 13篇 |
2018年 | 15篇 |
2017年 | 14篇 |
2016年 | 26篇 |
2015年 | 38篇 |
2014年 | 50篇 |
2013年 | 39篇 |
2012年 | 48篇 |
2011年 | 52篇 |
2010年 | 27篇 |
2009年 | 20篇 |
2008年 | 35篇 |
2007年 | 38篇 |
2006年 | 32篇 |
2005年 | 31篇 |
2004年 | 25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 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有638条查询结果,搜索用时 15 毫秒
81.
Madsen RK Lundstedt T Gabrielsson J Sennbro CJ Alenius GM Moritz T Rantapää-Dahlqvist S Trygg J 《Arthritis research & therapy》2011,13(1):R19
Introduction
The aim of this study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. 相似文献82.
83.
84.
Ros M Sorensen D Waagepetersen R Dupont-Nivet M SanCristobal M Bonnet JC Mallard J 《Genetics》2004,168(4):2089-2097
Phenotypic plasticity and canalization are important topics in quantitative genetics and evolution. Both concepts are related to environmental sensitivity. The latter can be modeled using a model with genetically structured environmental variance. This work reports the results of a genetic analysis of adult weight in the snail Helix aspersa. Several models of heterogeneous variance are fitted using a Bayesian, MCMC approach. Exploratory analyses using posterior predictive model checking and model comparisons based on the deviance information criterion favor a model postulating a genetically structured heterogeneous environmental variance. Our analysis provides a strong indication of a positive genetic correlation between additive genetic values affecting the mean and those affecting environmental variation of adult body weight. The possibility of manipulating environmental variance by selection is illustrated numerically using estimates of parameters derived from the snail data set. 相似文献
85.
Glycogen storage disease type Ib is caused by mutations in the glucose 6-phosphate transporter (G6PT) in the endoplasmic reticulum membrane in liver and kidney. Twenty-eight missense and two deletion mutations that cause the disease were previously shown to reduce or abolish the transporter's activity. However, the mechanisms by which these mutations impair transport remain unknown. On the basis of the recently determined crystal structure of its Escherichia coli homologue, the glycerol 3-phosphate transporter, we built a three-dimensional structural model of human G6PT by homology modeling. G6PT is proposed to consist of 12 transmembrane alpha-helices that are divided into N- and C-terminal domains, with the substrate-translocation pore located between the two domains and the substrate-binding site formed by R28 and K240 at the domain interface. The disease-causing mutations were found to occur at four types of positions: (I) in the substrate-translocation pore, (II) at the N-/C-terminal domain interface, (III) in the interior of the N- and C-terminal domains, and (IV) on the protein surface. Whereas class I mutations affect substrate binding directly, class II mutations, mostly involving changes in side chain size, charge, or both, hinder the conformational change required for substrate translocation. On the other hand, class III and class IV mutations, often introducing a charged residue into a helix bundle or at the protein-lipid interface, probably destabilize the protein. These results also suggest that G6PT operates by a similar antiport mechanism as its E. coli homologue, namely, the substrate binds at the N- and C-terminal domain interface and is then transported across the membrane via a rocker-switch type of movement of the two domains. 相似文献
86.
87.
88.
Statistical approaches for DNA barcoding 总被引:1,自引:0,他引:1
89.
Negahdar M Aukrust I Johansson BB Molnes J Molven A Matschinsky FM Søvik O Kulkarni RN Flatmark T Njølstad PR Bjørkhaug L 《Biochimica et biophysica acta》2012,1822(11):1705-1715
GCK-MODY, dominantly inherited mild fasting hyperglycemia, has been associated with >600 different mutations in the glucokinase (GK)-encoding gene (GCK). When expressed as recombinant pancreatic proteins, some mutations result in enzymes with normal/near-normal catalytic properties. The molecular mechanism(s) of GCK-MODY due to these mutations has remained elusive. Here, we aimed to explore the molecular mechanisms for two such catalytically 'normal' GCK mutations (S263P and G264S) in the F260-L270 loop of GK. When stably overexpressed in HEK293 cells and MIN6 β-cells, the S263P- and G264S-encoded mutations generated misfolded proteins with an increased rate of degradation (S263P>G264S) by the protein quality control machinery, and a propensity to self-associate (G264S>S263P) and form dimers (SDS resistant) and aggregates (partly Triton X-100 insoluble), as determined by pulse-chase experiments and subcellular fractionation. Thus, the GCK-MODY mutations S263P and G264S lead to protein misfolding causing destabilization, cellular dimerization/aggregation and enhanced rate of degradation. In silico predicted conformational changes of the F260-L270 loop structure are considered to mediate the dimerization of both mutant proteins by a domain swapping mechanism. Thus, similar properties may represent the molecular mechanisms for additional unexplained GCK-MODY mutations, and may also contribute to the disease mechanism in other previously characterized GCK-MODY inactivating mutations. 相似文献
90.
Africa is unique among the continents in having maintained an extraordinarily diverse and prolific megafauna spanning the Pleistocene-Holocene epochs. Little is known about the historical dynamics of this community and even less about the reasons for its unique persistence to modern times. We sequenced complete mitochondrial genomes from 43 Cape buffalo (Syncerus caffer caffer) to infer the demographic history of this large mammal. A combination of Bayesian skyline plots, simulations and Approximate Bayesian Computation (ABC) were used to distinguish population size dynamics from the confounding effect of population structure and identify the most probable demographic scenario. Our analyses revealed a late Pleistocene expansion phase concurrent with the human expansion between 80 000 and 10 000 years ago, refuting an adverse ecological effect of Palaeolithic humans on this quarry species, but also showed that the buffalo subsequently declined during the Holocene. The distinct two-phased dynamic inferred here suggests that a major ecological transition occurred in the Holocene. The timing of this transition coincides with the onset of drier conditions throughout tropical Africa following the Holocene Optimum (~9000-5000 years ago), but also with the explosive growth in human population size associated with the transition from the Palaeolithic to the Neolithic cultural stage. We evaluate each of these possible causal factors and their potential impact on the African megafauna, providing the first systematic assessment of megafauna dynamics on the only continent where large mammals remain abundant. 相似文献