首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2339篇
  免费   193篇
  2532篇
  2023年   4篇
  2022年   10篇
  2021年   33篇
  2020年   11篇
  2019年   14篇
  2018年   25篇
  2017年   25篇
  2016年   38篇
  2015年   108篇
  2014年   94篇
  2013年   117篇
  2012年   180篇
  2011年   161篇
  2010年   112篇
  2009年   114篇
  2008年   146篇
  2007年   160篇
  2006年   145篇
  2005年   133篇
  2004年   149篇
  2003年   168篇
  2002年   124篇
  2001年   34篇
  2000年   12篇
  1999年   38篇
  1998年   40篇
  1997年   33篇
  1996年   24篇
  1995年   33篇
  1994年   27篇
  1993年   23篇
  1992年   18篇
  1991年   20篇
  1990年   9篇
  1989年   22篇
  1988年   16篇
  1987年   9篇
  1986年   12篇
  1985年   6篇
  1984年   10篇
  1983年   9篇
  1982年   14篇
  1981年   8篇
  1979年   4篇
  1978年   9篇
  1977年   10篇
  1976年   4篇
  1974年   4篇
  1973年   2篇
  1966年   2篇
排序方式: 共有2532条查询结果,搜索用时 15 毫秒
71.

Background  

The rapid growth of the amount of publicly available reports on biomedical experimental results has recently caused a boost of text mining approaches for protein interaction extraction. Most approaches rely implicitly or explicitly on linguistic, i.e., lexical and syntactic, data extracted from text. However, only few attempts have been made to evaluate the contribution of the different feature types. In this work, we contribute to this evaluation by studying the relative importance of deep syntactic features, i.e., grammatical relations, shallow syntactic features (part-of-speech information) and lexical features. For this purpose, we use a recently proposed approach that uses support vector machines with structured kernels.  相似文献   
72.
The hypersensitive response has been mostly studied by molecular and biochemical methods after sample destruction. The development of imaging techniques allows the monitoring of physiological changes before any signs of cell death. Here, we follow the early steps of a hypersensitive-like response induced by the bacterial elicitor harpin in Nicotiana sp. We describe cytological modifications after inoculation of the harpin protein, using confocal fluorescence microscopy (CFM) and optical coherence tomography (OCT), an interferometric-based microscopy. The changes detected by CFM occurred 5 h after harpin infiltration and corresponded to a redistribution of the chloroplasts from the upper to the inner regions of the palisade mesophyll cells which could be related to a perturbation in the microtubule network. Using OCT, we were able to detect a decrease in chloroplast backscattered signal as early as 30 min after harpin infiltration. A simple physical model, which accounted for the structure and distribution of thylakoid membranes, suggested that this loss of scattering could be associated with a modification in the refractive index of the thylakoid membranes. Our OCT observations were correlated with a decrease in photosynthesis, emphasizing changes in chloroplast structure as one of the earliest hallmarks of plant hypersensitive cell death.  相似文献   
73.
74.
YKL-40 is a chitin-binding protein that is elevated in patients with various inflammatory conditions associated with ongoing remodeling. We investigated whether the levels of YKL-40 were up-regulated in the circulation and the airways of patients with chronic obstructive pulmonary disease (COPD), and whether it promoted the production of inflammatory mediators from macrophages. Serum, bronchoalveolar lavage (BAL), bronchial biopsies, lung tissue specimens, and alveolar macrophages from never-smokers (n = 15), smokers without COPD (n = 20), and smokers with COPD (n = 30) were assessed for YKL-40 levels and immunolocalization. In addition, YKL-40-induced mediator release from alveolar macrophages was examined. We found that smokers with COPD had elevated levels of YKL-40 in serum (p 相似文献   
75.
Infection of hepatocytes by Plasmodium falciparum sporozoites requires the host tetraspanin CD81. CD81 is also predicted to be a coreceptor, along with scavenger receptor BI (SR-BI), for hepatitis C virus. Using SR-BI-knockout, SR-BI-hypomorphic and SR-BI-transgenic primary hepatocytes, as well as specific SR-BI-blocking antibodies, we demonstrate that SR-BI significantly boosts hepatocyte permissiveness to P. falciparum, P. yoelii, and P. berghei entry and promotes parasite development. We show that SR-BI, but not the low-density lipoprotein receptor, acts as a major cholesterol provider that enhances Plasmodium infection. SR-BI regulates the organization of CD81 at the plasma membrane, mediating an arrangement that is highly permissive to penetration by sporozoites. Concomitantly, SR-BI upregulates the expression of the liver fatty-acid carrier L-FABP, a protein implicated in Plasmodium liver-stage maturation. These findings establish the mechanistic basis of the CD81-dependent Plasmodium sporozoite invasion pathway.  相似文献   
76.

Background  

Functional studies in model organisms, such as vertebrates and Drosophila, have shown that basic Helix-loop-Helix (bHLH) proteins have important roles in different steps of neurogenesis, from the acquisition of neural fate to the differentiation into specific neural cell types. However, these studies highlighted many differences in the expression and function of orthologous bHLH proteins during neural development between vertebrates and Drosophila. To understand how the functions of neural bHLH genes have evolved among bilaterians, we have performed a detailed study of bHLH genes during nervous system development in the polychaete annelid, Platynereis dumerilii, an organism which is evolutionary distant from both Drosophila and vertebrates.  相似文献   
77.
Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.  相似文献   
78.
HIV-1 infection is characterized by a progressive CD4 T cell depletion. It is now accepted that apoptosis of uninfected bystander CD4 T lymphocytes plays a major role in AIDS development. Viral envelope glycoproteins (Env) are mainly involved in inducing this cell death process, but the mechanisms triggered by HIV-1 leading to immunodeficiency are still poorly understood. Recently, we have demonstrated that autophagy is a prerequisite for Env-mediated apoptosis in uninfected CD4 T cells, underlining its role in HIV-1 infection. However, occurrence of autophagy in HIV-1-infected cells has not yet been described. Several hypotheses are discussed, based on the comparison with data from other viral infections.  相似文献   
79.
Innate immune system is the first line of host defense against invading microorganisms. It relies on a limited number of germline-encoded pattern recognition receptors that recognize conserved molecular structures of microbes, referred to as pathogen-/microbe-associated molecular patterns (PAMPs/MAMPs). Bacterial cell wall macroamphiphiles, namely Gram-negative bacteria lipopolysaccharide (LPS), Gram-positive bacteria lipoteichoic acid (LTA), lipoproteins and mycobacterial lipoglycans, are important molecules for the physiology of bacteria and evidently meet PAMP/MAMP criteria. They are well suited to innate immune recognition and constitute non-self signatures detected by the innate immune system to signal the presence of an infective agent. They are notably recognized via their lipid anchor by Toll-like receptors (TLRs) 4 or 2. Here, we review our current knowledge of the molecular bases of macroamphiphile recognition by TLRs, with a special emphasis on mycobacterial lipoglycan detection by TLR2.  相似文献   
80.
Celiac disease is a T cell-driven intolerance to wheat gluten. The gluten-derived T cell epitopes are proline-rich and thereby highly resistant to proteolytic degradation within the gastrointestinal tract. Oral supplementation with prolyl oligopeptidases has therefore been proposed as a potential therapeutic approach. The enzymes studied, however, have limitations as they are irreversibly inactivated by pepsin and acidic pH, both present in the stomach. As a consequence, these enzymes will fail to degrade gluten before it reaches the small intestine, the site where gluten induces inflammatory T cell responses that lead to celiac disease. We have now determined the usefulness of a newly identified prolyl endoprotease from Aspergillus niger for this purpose. Gluten and its peptic/tryptic digest were treated with prolyl endoprotease, and the destruction of the T cell epitopes was tested using mass spectrometry, T cell proliferation assays, ELISA, reverse-phase HPLC, SDS-PAGE, and Western blotting. We observed that the A. niger prolyl endoprotease works optimally at 4-5 pH, remains stable at 2 pH, and is completely resistant to digestion with pepsin. Moreover, the A. niger-derived enzyme efficiently degraded all tested T cell stimulatory peptides as well as intact gluten molecules. On average, the endoprotease from A. niger degraded gluten peptides 60 times faster than a prolyl oligopeptidase. Together these results indicate that the enzyme from A. niger efficiently degrades gluten proteins. Future studies are required to determine if the prolyl endoprotease can be used as an oral supplement to reduce gluten intake in patients.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号