全文获取类型
收费全文 | 2899篇 |
免费 | 245篇 |
出版年
2023年 | 9篇 |
2022年 | 33篇 |
2021年 | 46篇 |
2020年 | 31篇 |
2019年 | 44篇 |
2018年 | 52篇 |
2017年 | 36篇 |
2016年 | 67篇 |
2015年 | 140篇 |
2014年 | 169篇 |
2013年 | 171篇 |
2012年 | 243篇 |
2011年 | 229篇 |
2010年 | 114篇 |
2009年 | 117篇 |
2008年 | 177篇 |
2007年 | 178篇 |
2006年 | 156篇 |
2005年 | 158篇 |
2004年 | 171篇 |
2003年 | 157篇 |
2002年 | 144篇 |
2001年 | 39篇 |
2000年 | 23篇 |
1999年 | 35篇 |
1998年 | 48篇 |
1997年 | 39篇 |
1996年 | 25篇 |
1995年 | 27篇 |
1994年 | 22篇 |
1993年 | 28篇 |
1992年 | 19篇 |
1991年 | 15篇 |
1990年 | 22篇 |
1989年 | 17篇 |
1988年 | 13篇 |
1987年 | 14篇 |
1986年 | 8篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 13篇 |
1982年 | 12篇 |
1981年 | 6篇 |
1980年 | 12篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1974年 | 5篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1969年 | 3篇 |
排序方式: 共有3144条查询结果,搜索用时 31 毫秒
111.
Kristine von Bargen Mirella Scraba Ina Krmer Maren Ketterer Christian Nehls Sina Krokowski Urska Repnik Michaela Wittlich Anna Maaser Pia Zapka Madeleine Bunge Martin Schlesinger Gitta Huth Annette Klees Philipp Hansen Andreas Jeschke Gerd Bendas Olaf Utermhlen Gareth Griffiths Thomas Gutsmann Jens Wohlmann Albert Haas 《Cellular microbiology》2019,21(1)
Professional phagocytic cells such as macrophages are a central part of innate immune defence. They ingest microorganisms into membrane‐bound compartments (phagosomes), which acidify and eventually fuse with lysosomes, exposing their contents to a microbicidal environment. Gram‐positive Rhodococcus equi can cause pneumonia in young foals and in immunocompromised humans. The possession of a virulence plasmid allows them to subvert host defence mechanisms and to multiply in macrophages. Here, we show that the plasmid‐encoded and secreted virulence‐associated protein A (VapA) participates in exclusion of the proton‐pumping vacuolar‐ATPase complex from phagosomes and causes membrane permeabilisation, thus contributing to a pH‐neutral phagosome lumen. Using fluorescence and electron microscopy, we show that VapA is also transferred from phagosomes to lysosomes where it permeabilises the limiting membranes for small ions such as protons. This permeabilisation process is different from that of known membrane pore formers as revealed by experiments with artificial lipid bilayers. We demonstrate that, at 24 hr of infection, virulent R. equi is contained in a vacuole, which is enriched in lysosome material, yet possesses a pH of 7.2 whereas phagosomes containing a vapA deletion mutant have a pH of 5.8 and those with virulence plasmid‐less sister strains have a pH of 5.2. Experimentally neutralising the macrophage endocytic system allows avirulent R. equi to multiply. This observation is mirrored in the fact that virulent and avirulent R. equi multiply well in extracts of purified lysosomes at pH 7.2 but not at pH 5.1. Together these data indicate that the major function of VapA is to generate a pH‐neutral and hence growth‐promoting intracellular niche. VapA represents a new type of Gram‐positive virulence factor by trafficking from one subcellular compartment to another, affecting membrane permeability, excluding proton‐pumping ATPase, and consequently disarming host defences. 相似文献
112.
Tremblay LO Nagy Kovács E Daniels E Wong NK Sutton-Smith M Morris HR Dell A Marcinkiewicz E Seidah NG McKerlie C Herscovics A 《The Journal of biological chemistry》2007,282(4):2558-2566
There are three mammalian Golgi alpha1,2-mannosidases, encoded by different genes, that form Man5GlcNAc2 from Man(8-9)GlcNAc2 for the biosynthesis of hybrid and complex N-glycans. Northern blot analysis and in situ hybridization indicate that the three paralogs display distinct developmental and tissue-specific expression. The physiological role of Golgi alpha1,2-mannosidase IB was investigated by targeted gene ablation. The null mice have normal gross appearance at birth, but they display respiratory distress and die within a few hours. Histology of fetal lungs the day before birth indicate some delay in development, whereas neonatal lungs show extensive pulmonary hemorrhage in the alveolar region. No significant histopathological changes occur in other tissues. No remarkable ultrastructural differences are detected between wild type and null lungs. The membranes of a subset of bronchiolar epithelial cells are stained with lectins from Phaseolus vulgaris (leukoagglutinin and erythroagglutinin) and Datura stramonium in wild type lungs, but this staining disappears in lungs from null mice. Mass spectrometry of N-glycans from different tissues shows no significant changes in global N-glycans of null mice. Therefore, only a few glycoproteins required for normal lung function depend on alpha1,2-mannosidase IB for maturation. There are no apparent differences in the expression of several lung epithelial cell and endothelial cell markers between null and wild type mice. The alpha1,2-mannosidase IB null phenotype differs from phenotypes caused by ablation of other enzymes in N-glycan biosynthesis and from other mouse gene disruptions that affect pulmonary development and function. 相似文献
113.
Cline MS Smoot M Cerami E Kuchinsky A Landys N Workman C Christmas R Avila-Campilo I Creech M Gross B Hanspers K Isserlin R Kelley R Killcoyne S Lotia S Maere S Morris J Ono K Pavlovic V Pico AR Vailaya A Wang PL Adler A Conklin BR Hood L Kuiper M Sander C Schmulevich I Schwikowski B Warner GJ Ideker T Bader GD 《Nature protocols》2007,2(10):2366-2382
Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape. 相似文献
114.
115.
116.
117.
Elizabeth F. Dowler Annette Diehl Peter Schmieder Christoph Brockmann Jonathan Elkins Meera Soundararajan Hartmut Oschkinat Linda J. Ball 《Biomolecular NMR assignments》2007,1(1):95-97
We have assigned 1H, 15N and 13C resonances of the RGS domain from the human RGS14 protein, a multi-domain member of the RGS (Regulators of G-protein signalling)
family of proteins, important in the down-regulation of specific G-protein signalling pathways. 相似文献
118.
Fina A. S Kurreeman Leonid Padyukov Rute B Marques Steven J Schrodi Maria Seddighzadeh Gerrie Stoeken-Rijsbergen Annette H. M van der Helm-van Mil Cornelia F Allaart Willem Verduyn Jeanine Houwing-Duistermaat Lars Alfredsson Ann B Begovich Lars Klareskog Tom W. J Huizinga Rene E. M Toes 《PLoS medicine》2007,4(12)
119.
Andersen Julie Høgsgaard Tjørnhøj-Thomsen Tine Reventlow Susanne Davidsen Annette Sofie 《Culture, medicine and psychiatry》2019,43(3):425-441
Culture, Medicine, and Psychiatry - An increasing number of young adults in Denmark experience difficulties in completing their education and holding down a job. Many of these young adults have... 相似文献
120.
Phytoplasmas are cell wall‐less phytopathogenic bacteria which are associated with a disease in Rubus species known as Rubus stunt. Symptoms range from stunting, witches’ broom, small leaves, short internodes, enlarged sepals, phyllody and flower proliferation to fruit malformations. Phytoplasmas can be spread by vegetative propagation and by phloem‐feeding insect vectors. However, little is known about the spectrum and distribution of putative Rubus stunt insect vectors. In this study, a screening of putative insect vectors of Rubus stunt in raspberry plantations in southern and northern Germany was carried out during two successive years (2014 and 2015) with multiple sampling dates throughout the growing seasons. A total of 2,891 hemipteran insects were sorted, identified to family, genus or species level when possible, and a subset of 319 DNA samples containing a sum of 932 selected individuals representing all identified species, sampling locations and sampling dates were tested for phytoplasma DNA using qPCR. Altogether, eight DNA samples were positive for phytoplasma DNA, among them species from the genera Euscelidius, Macrosteles, Euscelis, Anaceratagalliaand Psammotettix. These data will form the basis for choosing and timing appropriate control measures against Rubus stunt and also for potential insect vector transmission experiments. 相似文献