全文获取类型
收费全文 | 2690篇 |
免费 | 246篇 |
国内免费 | 1篇 |
专业分类
2937篇 |
出版年
2024年 | 5篇 |
2023年 | 18篇 |
2022年 | 20篇 |
2021年 | 64篇 |
2020年 | 46篇 |
2019年 | 39篇 |
2018年 | 60篇 |
2017年 | 60篇 |
2016年 | 96篇 |
2015年 | 154篇 |
2014年 | 147篇 |
2013年 | 181篇 |
2012年 | 259篇 |
2011年 | 252篇 |
2010年 | 145篇 |
2009年 | 134篇 |
2008年 | 181篇 |
2007年 | 152篇 |
2006年 | 168篇 |
2005年 | 168篇 |
2004年 | 130篇 |
2003年 | 112篇 |
2002年 | 110篇 |
2001年 | 20篇 |
2000年 | 13篇 |
1999年 | 31篇 |
1998年 | 17篇 |
1997年 | 9篇 |
1996年 | 13篇 |
1995年 | 12篇 |
1994年 | 11篇 |
1993年 | 4篇 |
1992年 | 14篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1981年 | 3篇 |
1977年 | 3篇 |
1973年 | 3篇 |
1971年 | 3篇 |
1969年 | 3篇 |
1967年 | 4篇 |
1882年 | 2篇 |
1878年 | 2篇 |
排序方式: 共有2937条查询结果,搜索用时 15 毫秒
41.
42.
Leberg Samuel S Barriga Ramiro Bart Henry Olivo Alfredo Narasimhan Kaushik Karubian Jordan 《Environmental Biology of Fishes》2021,104(3):239-251
Environmental Biology of Fishes - Environmental conditions influence ecological processes that shape stream community diversity and abundance. Deforestation has the potential to limit available... 相似文献
43.
Yoana Rabanal-Ruiz Adam Byron Alexander Wirth Ralitsa Madsen Lucia Sedlackova Graeme Hewitt Glyn Nelson Julian Stingele Jimi C. Wills Tong Zhang Andr Zeug Reinhard Fssler Bart Vanhaesebroeck Oliver D.K. Maddocks Evgeni Ponimaskin Bernadette Carroll Viktor I. Korolchuk 《The Journal of cell biology》2021,220(5)
The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogenic and stress signals to control growth and metabolism. Activation of mTORC1 by amino acids and growth factors involves recruitment of the complex to the lysosomal membrane and is further supported by lysosome distribution to the cell periphery. Here, we show that translocation of lysosomes toward the cell periphery brings mTORC1 into proximity with focal adhesions (FAs). We demonstrate that FAs constitute discrete plasma membrane hubs mediating growth factor signaling and amino acid input into the cell. FAs, as well as the translocation of lysosome-bound mTORC1 to their vicinity, contribute to both peripheral and intracellular mTORC1 activity. Conversely, lysosomal distribution to the cell periphery is dispensable for the activation of mTORC1 constitutively targeted to FAs. This study advances our understanding of spatial mTORC1 regulation by demonstrating that the localization of mTORC1 to FAs is both necessary and sufficient for its activation by growth-promoting stimuli. 相似文献
44.
45.
Ljudmilla Borisjuk Thomas Neuberger J?rg Schwender Nicolas Heinzel Stephanie Sunderhaus Johannes Fuchs Jordan O. Hay Henning Tschiersch Hans-Peter Braun Peter Denolf Bart Lambert Peter M. Jakob Hardy Rolletschek 《The Plant cell》2013,25(5):1625-1640
Constrained to develop within the seed, the plant embryo must adapt its shape and size to fit the space available. Here, we demonstrate how this adjustment shapes metabolism of photosynthetic embryo. Noninvasive NMR-based imaging of the developing oilseed rape (Brassica napus) seed illustrates that, following embryo bending, gradients in lipid concentration became established. These were correlated with the local photosynthetic electron transport rate and the accumulation of storage products. Experimentally induced changes in embryo morphology and/or light supply altered these gradients and were accompanied by alterations in both proteome and metabolome. Tissue-specific metabolic models predicted that the outer cotyledon and hypocotyl/radicle generate the bulk of plastidic reductant/ATP via photosynthesis, while the inner cotyledon, being enclosed by the outer cotyledon, is forced to grow essentially heterotrophically. Under field-relevant high-light conditions, major contribution of the ribulose-1,5-bisphosphate carboxylase/oxygenase–bypass to seed storage metabolism is predicted for the outer cotyledon and the hypocotyl/radicle only. Differences between in vitro– versus in planta–grown embryos suggest that metabolic heterogeneity of embryo is not observable by in vitro approaches. We conclude that in vivo metabolic fluxes are locally regulated and connected to seed architecture, driving the embryo toward an efficient use of available light and space. 相似文献
46.
Zhao Zhang H. Peter van Esse Mireille van Damme Emilie F. Fradin Chun‐Ming Liu Bart P. H. J. Thomma 《Molecular Plant Pathology》2013,14(7):719-727
The recognition of pathogen effectors by plant immune receptors leads to the activation of immune responses that often include a hypersensitive response (HR): rapid and localized host cell death surrounding the site of attempted pathogen ingress. We have demonstrated previously that the recognition of the Verticillium dahliae effector protein Ave1 by the tomato immune receptor Ve1 triggers an HR in tomato and tobacco. Furthermore, we have demonstrated that tomato Ve1 provides Verticillium resistance in Arabidopsis upon Ave1 recognition. In this study, we investigated whether the co‐expression of Ve1 and Ave1 in Arabidopsis results in an HR, which could facilitate a forward genetics screen. Surprisingly, we found that the co‐expression of Ve1 and Ave1 does not induce an HR in Arabidopsis. These results suggest that an HR may occur as a consequence of Ve1/Ave1‐induced immune signalling in tomato and tobacco, but is not absolutely required for Verticillium resistance. 相似文献
47.
Pedro Casado Maria P Alcolea Francesco Iorio Juan-Carlos Rodríguez-Prados Bart Vanhaesebroeck Julio Saez-Rodriguez Simon Joel Pedro R Cutillas 《Genome biology》2013,14(4):R37
Background
Tumor classification based on their predicted responses to kinase inhibitors is a major goal for advancing targeted personalized therapies. Here, we used a phosphoproteomic approach to investigate biological heterogeneity across hematological cancer cell lines including acute myeloid leukemia, lymphoma, and multiple myeloma.Results
Mass spectrometry was used to quantify 2,000 phosphorylation sites across three acute myeloid leukemia, three lymphoma, and three multiple myeloma cell lines in six biological replicates. The intensities of the phosphorylation sites grouped these cancer cell lines according to their tumor type. In addition, a phosphoproteomic analysis of seven acute myeloid leukemia cell lines revealed a battery of phosphorylation sites whose combined intensities correlated with the growth-inhibitory responses to three kinase inhibitors with remarkable correlation coefficients and fold changes (> 100 between the most resistant and sensitive cells). Modeling based on regression analysis indicated that a subset of phosphorylation sites could be used to predict response to the tested drugs. Quantitative analysis of phosphorylation motifs indicated that resistant and sensitive cells differed in their patterns of kinase activities, but, interestingly, phosphorylations correlating with responses were not on members of the pathway being targeted; instead, these mainly were on parallel kinase pathways.Conclusion
This study reveals that the information on kinase activation encoded in phosphoproteomics data correlates remarkably well with the phenotypic responses of cancer cells to compounds that target kinase signaling and could be useful for the identification of novel markers of resistance or sensitivity to drugs that target the signaling network. 相似文献48.
Simon Rinaldi Kathryn M. Brennan Gabriela Kalna Christa Walgaard Pieter van Doorn Bart C. Jacobs Robert K. Yu Jan-Eric Mansson Carl S. Goodyear Hugh J. Willison 《PloS one》2013,8(12)
Autoantibodies are infrequently detected in the sera of patients with the demyelinating form of Guillain-Barré syndrome most commonly encountered in the Western world, despite abundant circumstantial evidence suggesting their existence. We hypothesised that antibody specificities reliant on the cis interactions of neighbouring membrane glycolipids could explain this discrepancy, and would not have been detected by traditional serological assays using highly purified preparations of single gangliosides. To assess the frequency of glycolipid complex antibodies in a Western European cohort of patients GBS we used a newly developed combinatorial glycoarray methodology to screen against large range of antigens (11 gangliosides, 8 other single glycolipids and 162 heterodimeric glycolipid complexes). Serum samples of 181 patients from a geographically defined, Western European cohort of GBS cases were analysed, along with 161 control sera. Serum IgG binding to single gangliosides was observed in 80.0% of axonal GBS cases, but in only 11.8% of cases with demyelinating electrophysiology. The inclusion of glycolipid complexes increased the positivity rate in demyelinating disease to 62.4%. There were 40 antigens with statistically significantly increased binding intensities in GBS as compared to healthy control sera. Of these, 7 complex antigens and 1 single ganglioside also produced statistically significantly increased binding intensities in GBS versus neurological disease controls. The detection of antibodies against specific complexes was associated with particular clinical features including disease severity, requirement for mechanical ventilation, and axonal electrophysiology. This study demonstrates that while antibodies against single gangliosides are often found in cases with axonal-type electrophysiology, antibodies against glycolipid complexes predominate in cases with demyelinating electrophysiology, providing a more robust serum biomarker than has ever been previously available for such cases. This work confirms the activation of the humoral immune system in the dysimmune disease process in GBS, and correlates patterns of antigen recognition with different clinical features. 相似文献
49.
50.
Marcel Janse Bert-Jan F. de Rooij Bart van Hoek Arie P. van den Berg Robert J. Porte Hans Blokzijl Minneke J. Coenraad Bouke G. Hepkema Alexander F. Schaapherder Jan Ringers Rinse K. Weersma Hein W. Verspaget 《PloS one》2013,8(8)