全文获取类型
收费全文 | 1883篇 |
免费 | 155篇 |
出版年
2023年 | 3篇 |
2022年 | 15篇 |
2021年 | 26篇 |
2020年 | 14篇 |
2019年 | 19篇 |
2018年 | 24篇 |
2017年 | 21篇 |
2016年 | 44篇 |
2015年 | 73篇 |
2014年 | 92篇 |
2013年 | 101篇 |
2012年 | 161篇 |
2011年 | 147篇 |
2010年 | 89篇 |
2009年 | 99篇 |
2008年 | 121篇 |
2007年 | 136篇 |
2006年 | 114篇 |
2005年 | 122篇 |
2004年 | 94篇 |
2003年 | 101篇 |
2002年 | 95篇 |
2001年 | 28篇 |
2000年 | 15篇 |
1999年 | 25篇 |
1998年 | 26篇 |
1997年 | 25篇 |
1996年 | 24篇 |
1995年 | 27篇 |
1994年 | 22篇 |
1993年 | 18篇 |
1992年 | 24篇 |
1991年 | 8篇 |
1990年 | 13篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1968年 | 4篇 |
1964年 | 3篇 |
排序方式: 共有2038条查询结果,搜索用时 125 毫秒
161.
162.
163.
164.
Hecht I Skoge ML Charest PG Ben-Jacob E Firtel RA Loomis WF Levine H Rappel WJ 《PLoS computational biology》2011,7(6):e1002044
Many eukaryotic cells are able to crawl on surfaces and guide their motility based on environmental cues. These cues are interpreted by signaling systems which couple to cell mechanics; indeed membrane protrusions in crawling cells are often accompanied by activated membrane patches, which are localized areas of increased concentration of one or more signaling components. To determine how these patches are related to cell motion, we examine the spatial localization of RasGTP in chemotaxing Dictyostelium discoideum cells under conditions where the vertical extent of the cell was restricted. Quantitative analyses of the data reveal a high degree of spatial correlation between patches of activated Ras and membrane protrusions. Based on these findings, we formulate a model for amoeboid cell motion that consists of two coupled modules. The first module utilizes a recently developed two-component reaction diffusion model that generates transient and localized areas of elevated concentration of one of the components along the membrane. The activated patches determine the location of membrane protrusions (and overall cell motion) that are computed in the second module, which also takes into account the cortical tension and the availability of protrusion resources. We show that our model is able to produce realistic amoeboid-like motion and that our numerical results are consistent with experimentally observed pseudopod dynamics. Specifically, we show that the commonly observed splitting of pseudopods can result directly from the dynamics of the signaling patches. 相似文献
165.
Graham NA Chabanet P Evans RD Jennings S Letourneur Y Aaron Macneil M McClanahan TR Ohman MC Polunin NV Wilson SK 《Ecology letters》2011,14(4):341-348
With rapidly increasing rates of contemporary extinction, predicting extinction vulnerability and identifying how multiple stressors drive non-random species loss have become key challenges in ecology. These assessments are crucial for avoiding the loss of key functional groups that sustain ecosystem processes and services. We developed a novel predictive framework of species extinction vulnerability and applied it to coral reef fishes. Although relatively few coral reef fishes are at risk of global extinction from climate disturbances, a negative convex relationship between fish species locally vulnerable to climate change vs. fisheries exploitation indicates that the entire community is vulnerable on the many reefs where both stressors co-occur. Fishes involved in maintaining key ecosystem functions are more at risk from fishing than climate disturbances. This finding is encouraging as local and regional commitment to fisheries management action can maintain reef ecosystem functions pending progress towards the more complex global problem of stabilizing the climate. 相似文献
166.
Rival T Macchi M Arnauné-Pelloquin L Poidevin M Maillet F Richard F Fatmi A Belenguer P Royet J 《EMBO reports》2011,12(3):223-230
Mitochondria are highly dynamic organelles that can change in number and morphology during cell cycle, development or in response to extracellular stimuli. These morphological dynamics are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Genetic approaches have identified a cohort of conserved proteins that form the core of mitochondrial remodelling machineries. Mitofusins (MFNs) and OPA1 proteins are dynamin-related GTPases that are required for outer- and inner-mitochondrial membrane fusion respectively whereas dynamin-related protein 1 (DRP1) is the master regulator of mitochondrial fission. We demonstrate here that the Drosophila PMI gene and its human orthologue TMEM11 encode mitochondrial inner-membrane proteins that regulate mitochondrial morphogenesis. PMI-mutant cells contain a highly condensed mitochondrial network, suggesting that PMI has either a pro-fission or an anti-fusion function. Surprisingly, however, epistatic experiments indicate that PMI shapes the mitochondria through a mechanism that is independent of drp1 and mfn. This shows that mitochondrial networks can be shaped in higher eukaryotes by at least two separate pathways: one PMI-dependent and one DRP1/MFN-dependent. 相似文献
167.
Thirant C Varlet P Lipecka J Le Gall M Broussard C Chafey P Studler JM Lacombe J Lions S Guillaudeau A Camoin L Daumas-Duport C Junier MP Chneiweiss H 《Proteomics》2011,11(21):4139-4154
Gliomas are primary tumors of the human central nervous system with unknown mechanisms of progression. Isocitrate dehydrogenase-1 (IDH1) mutation is frequent in diffuse gliomas such as oligodendrogliomas. To gain insights into the physiopathology of oligodendrogliomas that have a better prognosis than other diffuse gliomas, we combined microdissection, 2-D DIGE and MS/MS focusing on proteome alterations associated with IDH1 mutation. We first compared tumor tissues (TT) and minimally infiltrated parenchymal tissues (MIT) of four IDH1-mutated oligodendrogliomas to verify whether proteins specific to oligodendroglioma tumor cells could be identified from one patient to another. This study resulted in identification of 68 differentially expressed proteins, with functions related to growth of tumor cells in a nervous parenchyma. We then looked for proteins distinctly expressed in TT harboring either mutant (oligodendrogliomas, n=4) or wild-type IDH1 (oligodendroglial component of malignant glio-neuronal tumors, n=4). This second analysis resulted in identification of distinct proteome patterns composed of 42 proteins. Oligodendrogliomas with a mutant IDH1 had noteworthy enhanced expression of enzymes controlling aerobic glycolysis and detoxification, and anti-apoptosis proteins. In addition, the mutant IDH1 migrated differently from the wild-type IDH1 form. Comparative proteomic analysis might thus be suitable to identify proteome alterations associated with a well-defined mutation. 相似文献
168.
Vermachova M Purkrtova Z Santrucek J Jolivet P Chardot T Kodicek M 《Proteomics》2011,11(16):3430-3434
Plant seed oil bodies, subcellular lipoprotein inclusions providing storage reserves, are composed of a neutral lipid core surrounded by a phospholipid monolayer with several integrated proteins that play a significant role in stabilization of the particles and probably also in lipid mobilization. Oil bodies' proteins are generally very hydrophobic, due to the long uncharged sequences anchoring them into the lipid core, which makes them extremely difficult to handle and to digest successfully. Although oil bodies have been intensively studied during last decades, not all their proteins have been identified yet. To overcome the problems connected with their identification, a method based on SDS-PAGE, in-gel digestion and LC-MS/MS analysis was used. Digestion was carried out with trypsin and chymotrypsin, single or in combination, which increased significantly the number of identified peptides, namely the hydrophobic ones. Thanks to this methodology it was possible to achieve an extensive coverage of proteins studied, to analyze their N-terminal modifications and moreover, to detect four new oil bodies' protein isoforms, which demonstrates the complexity of oil bodies' protein composition. 相似文献
169.
Background
The objectives of this study were to determine the capacity of BED incidence testing to a) estimate the effect of a HIV prevention intervention and b) provide adequate statistical power, when used among young people from sub-Saharan African settings with high HIV incidence rates.Methods
Firstly, after having elaborated plausible scenarios based on empirical data and the characteristics of the BED HIV-1 Capture EIA (BED) assay, we conducted statistical calculations to determine the BED theoretical power and HIV incidence rate ratio (IRR) associated with an intervention when using BED incidence testing. Secondly, we simulated a cross-sectional study conducted in a population among whom an HIV intervention was rolled out. Simulated data were analyzed using a log-linear Poisson model to recalculate the IRR and its confidence interval, and estimate the BED practical power. Calculations were conducted with and without corrections for misclassifications.Results
Calculations showed that BED incidence testing can yield a BED theoretical power of 75% or more of the power that can be obtained in a classical cohort study conducted over a duration equal to the BED window period. Statistical analyses using simulated populations showed that the effect of a prevention intervention can be estimated with precision using classical statistical analysis of BED incidence testing data, even with an imprecise knowledge of the characteristics of the BED assay. The BED practical power was lower but of the same magnitude as the BED theoretical power.Conclusions
BED incidence testing can be applied to reasonably small samples to achieve good statistical power when used among young people to estimate IRR. 相似文献170.
Thirant C Bessette B Varlet P Puget S Cadusseau J Tavares Sdos R Studler JM Silvestre DC Susini A Villa C Miquel C Bogeas A Surena AL Dias-Morais A Léonard N Pflumio F Bièche I Boussin FD Sainte-Rose C Grill J Daumas-Duport C Chneiweiss H Junier MP 《PloS one》2011,6(1):e16375