全文获取类型
收费全文 | 2649篇 |
免费 | 183篇 |
国内免费 | 4篇 |
出版年
2023年 | 15篇 |
2022年 | 16篇 |
2021年 | 38篇 |
2020年 | 30篇 |
2019年 | 35篇 |
2018年 | 39篇 |
2017年 | 30篇 |
2016年 | 84篇 |
2015年 | 120篇 |
2014年 | 155篇 |
2013年 | 170篇 |
2012年 | 208篇 |
2011年 | 223篇 |
2010年 | 113篇 |
2009年 | 114篇 |
2008年 | 156篇 |
2007年 | 171篇 |
2006年 | 152篇 |
2005年 | 141篇 |
2004年 | 89篇 |
2003年 | 125篇 |
2002年 | 93篇 |
2001年 | 14篇 |
2000年 | 23篇 |
1999年 | 17篇 |
1998年 | 22篇 |
1997年 | 21篇 |
1996年 | 14篇 |
1995年 | 15篇 |
1994年 | 14篇 |
1993年 | 22篇 |
1992年 | 23篇 |
1991年 | 20篇 |
1990年 | 25篇 |
1989年 | 16篇 |
1988年 | 19篇 |
1987年 | 20篇 |
1986年 | 23篇 |
1985年 | 14篇 |
1984年 | 13篇 |
1983年 | 20篇 |
1982年 | 20篇 |
1980年 | 13篇 |
1979年 | 21篇 |
1978年 | 15篇 |
1975年 | 8篇 |
1973年 | 8篇 |
1972年 | 9篇 |
1971年 | 10篇 |
1969年 | 8篇 |
排序方式: 共有2836条查询结果,搜索用时 15 毫秒
191.
Deepak Jain Gesine Weber Daniel Eberhard Amir E. Mehana Jan Eglinger Alena Welters Barbara Bartosinska Kay Jeruschke Jürgen Weiss Günter P?th Hiroyoshi Ariga Jochen Seufert Eckhard Lammert 《PloS one》2015,10(9)
A hallmark feature of type 1 and type 2 diabetes mellitus is the progressive dysfunction and loss of insulin-producing pancreatic beta cells, and inflammatory cytokines are known to trigger beta cell death. Here we asked whether the anti-oxidant protein DJ-1 encoded by the Parkinson’s disease gene PARK7 protects islet cells from cytokine- and streptozotocin-mediated cell death. Wild type and DJ-1 knockout mice (KO) were treated with multiple low doses of streptozotocin (MLDS) to induce inflammatory beta cell stress and cell death. Subsequently, glucose tolerance tests were performed, and plasma insulin as well as fasting and random blood glucose concentrations were monitored. Mitochondrial morphology and number of insulin granules were quantified in beta cells. Moreover, islet cell damage was determined in vitro after streptozotocin and cytokine treatment of isolated wild type and DJ-1 KO islets using calcein AM/ethidium homodimer-1 staining and TUNEL staining. Compared to wild type mice, DJ-1 KO mice became diabetic following MLDS treatment. Insulin concentrations were substantially reduced, and fasting blood glucose concentrations were significantly higher in MLDS-treated DJ-1 KO mice compared to equally treated wild type mice. Rates of beta cell apoptosis upon MLDS treatment were twofold higher in DJ-1 KO mice compared to wild type mice, and in vitro inflammatory cytokines led to twice as much beta cell death in pancreatic islets from DJ-1 KO mice versus those of wild type mice. In conclusion, this study identified the anti-oxidant protein DJ-1 as being capable of protecting pancreatic islet cells from cell death induced by an inflammatory and cytotoxic setting. 相似文献
192.
Validating Solution Ensembles from Molecular Dynamics Simulation by Wide-Angle X-ray Scattering Data
Wide-angle x-ray scattering (WAXS) experiments of biomolecules in solution have become increasingly popular because of technical advances in light sources and detectors. However, the structural interpretation of WAXS profiles is problematic, partly because accurate calculations of WAXS profiles from structural models have remained challenging. In this work, we present the calculation of WAXS profiles from explicit-solvent molecular dynamics (MD) simulations of five different proteins. Using only a single fitting parameter that accounts for experimental uncertainties because of the buffer subtraction and dark currents, we find excellent agreement to experimental profiles both at small and wide angles. Because explicit solvation eliminates free parameters associated with the solvation layer or the excluded solvent, which would require fitting to experimental data, we minimize the risk of overfitting. We further find that the influence from water models and protein force fields on calculated profiles are insignificant up to q ≈ 15 nm?1. Using a series of simulations that allow increasing flexibility of the proteins, we show that incorporating thermal fluctuations into the calculations significantly improves agreement with experimental data, demonstrating the importance of protein dynamics in the interpretation of WAXS profiles. In addition, free MD simulations up to one microsecond suggest that the calculated profiles are highly sensitive with respect to minor conformational rearrangements of proteins, such as an increased flexibility of a loop or an increase of the radius of gyration by < 1%. The present study suggests that quantitative comparison between MD simulations and experimental WAXS profiles emerges as an accurate tool to validate solution ensembles of biomolecules. 相似文献
193.
Liquid films on shake flask walls explain increasing maximum oxygen transfer capacities with elevating viscosity
下载免费PDF全文
![点击此处可从《Biotechnology and bioengineering》网站下载免费的PDF全文](/ch/ext_images/free.gif)
194.
Gu C Yaddanapudi S Weins A Osborn T Reiser J Pollak M Hartwig J Sever S 《The EMBO journal》2010,29(21):3593-3606
The large GTPase dynamin assembles into higher order structures that are thought to promote endocytosis. Dynamin also regulates the actin cytoskeleton through an unknown, GTPase-dependent mechanism. Here, we identify a highly conserved site in dynamin that binds directly to actin filaments and aligns them into bundles. Point mutations in the actin-binding domain cause aberrant membrane ruffling and defective actin stress fibre formation in cells. Short actin filaments promote dynamin assembly into higher order structures, which in turn efficiently release the actin-capping protein (CP) gelsolin from barbed actin ends in vitro, allowing for elongation of actin filaments. Together, our results support a model in which assembled dynamin, generated through interactions with short actin filaments, promotes actin polymerization via displacement of actin-CPs. 相似文献
195.
196.
Li Wang Xin-ping Qi Qiao-ping Xiang Jochen Heinrichs Harald Schneider Xian-chun Zhang 《Molecular phylogenetics and evolution》2010,54(1):211-225
Phylogenetic relationships within the paleotropical genus Lepisorus (Polypodiaceae) were investigated using plastid DNA sequences from four regions: rbcL, rps4 and rps4-trnS IGS, trnL intron plus trnL-F IGS, rbcL-atpB IGS. Over 4000 nucleotides were sequenced for 77 specimens belonging to 54 species. Each cpDNA region was analyzed separately and combined into a single dataset. All phylogenetic analyses, maximum parsimony, maximum likelihood and Bayesian Inference of phylogeny, revealed the paraphyly of Lepisorus with the monotypic Drymotaenium miyoshianum and of the paleotropical genus Belvisia nested within the Lepisorus clade. Nine well-supported major clades were found. The phylogenetic results provided new evidence for the sectional classification of Lepisorus. The evolution of three morphological characters, clathrateness of rhizome scales, margin of rhizome scales and defoliated leaves, and the evolution of the karyotype, were reconstructed to identify lineage specific phenotypic character states or combination of characters. Unique character combinations, rather than synapomorphies, were found to be of systematic value in sectional delimitation. The variation of chromosome numbers is largely due to a single aneuploidy event instead of a stepwise reduction during the evolutionary history of this genus. 相似文献
197.
198.
Ramaiya M Johnson MG Shaw B Heinrichs J Hentschel J von Konrat M Davison PG Shaw AJ 《American journal of botany》2010,97(10):1707-1718
? Premise of the study: The Frullania tamarisci complex includes eight Holarctic liverwort species. One of these, F. asagrayana, is distributed broadly throughout eastern North America from Canada to the Gulf Coast. Preliminary genetic data suggested that the species includes two groups of populations. This study was designed to test whether the two groups are reproductively isolated biological species. ? Methods: Eighty-eight samples from across the range of F. asagrayana, plus 73 samples from one population, were genotyped for 13 microsatellite loci. Sequences for two plastid loci and nrITS were obtained from 13 accessions. Genetic data were analyzed using coalescent models and Bayesian inference. ? Key results: Frullania asagrayana is sequence-invariant at the two plastid loci and ITS2, but two clear groups were resolved by microsatellites. The two groups are largely reproductively isolated, but there is a low level of gene flow from the southern to the northern group. No gene flow was detected in the other direction. A local population was heterogeneous but displayed strong genetic structure. ? Conclusions: The genetic structure of F. asagrayana in eastern North America reflects morphologically cryptic differentiation between reproductively isolated groups of populations, near-panmixis within groups, and clonal propagation at local scales. Reproductive isolation between groups that are invariant at the level of nucleotide sequences shows that caution must be exercised in making taxonomic and evolutionary inferences from reciprocal monophyly (or lack thereof) between putative species. 相似文献
199.