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31.
AMPKα1‐LDH pathway regulates muscle stem cell self‐renewal by controlling metabolic homeostasis 下载免费PDF全文
Marine Theret Gaëtan Juban Sabrina Ben Larbi Michèle Weiss‐Gayet Laurent Bultot Marc Foretz Dominique Desplanches Pascual Sanz Zizhao Zang Lin Yang Guillaume Vial Benoit Viollet Kei Sakamoto Anne Brunet Bénédicte Chazaud Rémi Mounier 《The EMBO journal》2017,36(13):1946-1962
Control of stem cell fate to either enter terminal differentiation versus returning to quiescence (self‐renewal) is crucial for tissue repair. Here, we showed that AMP‐activated protein kinase (AMPK), the master metabolic regulator of the cell, controls muscle stem cell (MuSC) self‐renewal. AMPKα1?/? MuSCs displayed a high self‐renewal rate, which impairs muscle regeneration. AMPKα1?/? MuSCs showed a Warburg‐like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPKα1. LDH, which is a non‐limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPKα1?/? phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPKα1?/? MuSC self‐renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPKα1/LDH pathway, emphasizing the importance of metabolism in stem cell fate. 相似文献
32.
Toward a Low‐Cost Artificial Leaf: Driving Carbon‐Based and Bifunctional Catalyst Electrodes with Solution‐Processed Perovskite Photovoltaics 下载免费PDF全文
Tiva Sharifi Christian Larsen Jia Wang Wai Ling Kwong Eduardo Gracia‐Espino Guillaume Mercier Johannes Messinger Thomas Wågberg Ludvig Edman 《Liver Transplantation》2016,6(20)
Molecular hydrogen can be generated renewably by water splitting with an “artificial‐leaf device”, which essentially comprises two electrocatalyst electrodes immersed in water and powered by photovoltaics. Ideally, this device should operate efficiently and be fabricated with cost‐efficient means using earth‐abundant materials. Here, a lightweight electrocatalyst electrode, comprising large surface‐area NiCo2O4 nanorods that are firmly anchored onto a carbon–paper current collector via a dense network of nitrogen‐doped carbon nanotubes is presented. This electrocatalyst electrode is bifunctional in that it can efficiently operate as both anode and cathode in the same alkaline solution, as quantified by a delivered current density of 10 mA cm?2 at an overpotential of 400 mV for each of the oxygen and hydrogen evolution reactions. By driving two such identical electrodes with a solution‐processed thin‐film perovskite photovoltaic assembly, a wired artificial‐leaf device is obtained that features a Faradaic H2 evolution efficiency of 100%, and a solar‐to‐hydrogen conversion efficiency of 6.2%. A detailed cost analysis is presented, which implies that the material‐payback time of this device is of the order of 100 days. 相似文献
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ER–mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem‐like cells 下载免费PDF全文
Valentina Chiusolo Guillaume Jacquemin Emma Boydell Sebastian Zamorano Cristina Riccadonna Serena Pellegatta Nicolas Hulo Valérie Dutoit Madiha Derouazi Pierre Yves Dietrich Paul R Walker Denis Martinvalet 《The EMBO journal》2017,36(11):1493-1512
Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem‐like cells (GSC) being more sensitive to cytotoxic lymphocyte‐mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER–mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER–mitochondria contacts compared to GDCs. Forced ER–mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER–mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. 相似文献
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In parasites, host specificity may result either from restricted dispersal capacity or from fixed coevolutionary host-parasite adaptations. Knowledge of those proximal mechanisms leading to particular host specificity is fundamental to understand host-parasite interactions and potential coevolution of parasites and hosts. The relative importance of these two mechanisms was quantified through infection and cross-infection experiments using mites and bats as a model. Monospecific pools of parasitic mites (Spinturnix myoti and S. andegavinus) were subjected either to individual bats belonging to their traditional, native bat host species, or to another substitute host species within the same bat genus (Myotis). The two parasite species reacted differently to these treatments. S. myoti exhibited a clear preference for, and had a higher fitness on, its native host, Myotis myotis. In contrast, S. andegavinus showed no host choice, although its fitness was higher on its native host M. daubentoni. The causal mechanisms mediating host specificity can apparently differ within closely related host-parasite systems. 相似文献
38.
Fei Yao Pramila N. Ariyaratne Axel M. Hillmer Wah Heng Lee Guoliang Li Audrey S. M. Teo Xing Yi Woo Zhenshui Zhang Jieqi P. Chen Wan Ting Poh Kelson F. B. Zawack Chee Seng Chan See Ting Leong Say Chuan Neo Poh Sum D. Choi Song Gao Niranjan Nagarajan Hervé Thoreau Atif Shahab Xiaoan Ruan Valère Cacheux-Rataboul Chia-Lin Wei Guillaume Bourque Wing-Kin Sung Edison T. Liu Yijun Ruan 《PloS one》2012,7(9)
Structural variations (SVs) contribute significantly to the variability of the human genome and extensive genomic rearrangements are a hallmark of cancer. While genomic DNA paired-end-tag (DNA-PET) sequencing is an attractive approach to identify genomic SVs, the current application of PET sequencing with short insert size DNA can be insufficient for the comprehensive mapping of SVs in low complexity and repeat-rich genomic regions. We employed a recently developed procedure to generate PET sequencing data using large DNA inserts of 10–20 kb and compared their characteristics with short insert (1 kb) libraries for their ability to identify SVs. Our results suggest that although short insert libraries bear an advantage in identifying small deletions, they do not provide significantly better breakpoint resolution. In contrast, large inserts are superior to short inserts in providing higher physical genome coverage for the same sequencing cost and achieve greater sensitivity, in practice, for the identification of several classes of SVs, such as copy number neutral and complex events. Furthermore, our results confirm that large insert libraries allow for the identification of SVs within repetitive sequences, which cannot be spanned by short inserts. This provides a key advantage in studying rearrangements in cancer, and we show how it can be used in a fusion-point-guided-concatenation algorithm to study focally amplified regions in cancer. 相似文献
39.
Jan Plue Pieter De Frenne Kamal Acharya Jrg Brunet Olivier Chabrerie Guillaume Decocq Martin Diekmann Bente J. Graae Thilo Heinken Martin Hermy Annette Kolb Isgard Lemke Jaan Liira Tobias Naaf Anna Shevtsova Kris Verheyen Monika Wulf Sara A. O. Cousins 《Global Ecology and Biogeography》2013,22(10):1106-1117
40.
Guillaume Martin Sylvain Gandon 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2010,365(1548):1953-1963
The lethal mutagenesis hypothesis states that within-host populations of pathogens can be driven to extinction when the load of deleterious mutations is artificially increased with a mutagen, and becomes too high for the population to be maintained. Although chemical mutagens have been shown to lead to important reductions in viral titres for a wide variety of RNA viruses, the theoretical underpinnings of this process are still not clearly established. A few recent models sought to describe lethal mutagenesis but they often relied on restrictive assumptions. We extend this earlier work in two novel directions. First, we derive the dynamics of the genetic load in a multivariate Gaussian fitness landscape akin to classical quantitative genetics models. This fitness landscape yields a continuous distribution of mutation effects on fitness, ranging from deleterious to beneficial (i.e. compensatory) mutations. We also include an additional class of lethal mutations. Second, we couple this evolutionary model with an epidemiological model accounting for the within-host dynamics of the pathogen. We derive the epidemiological and evolutionary equilibrium of the system. At this equilibrium, the density of the pathogen is expected to decrease linearly with the genomic mutation rate U. We also provide a simple expression for the critical mutation rate leading to extinction. Stochastic simulations show that these predictions are accurate for a broad range of parameter values. As they depend on a small set of measurable epidemiological and evolutionary parameters, we used available information on several viruses to make quantitative and testable predictions on critical mutation rates. In the light of this model, we discuss the feasibility of lethal mutagenesis as an efficient therapeutic strategy. 相似文献