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   2335篇
  免费   171篇
  2506篇
  2024年   3篇
  2023年   11篇
  2022年   33篇
  2021年   59篇
  2020年   32篇
  2019年   54篇
  2018年   80篇
  2017年   52篇
  2016年   92篇
  2015年   117篇
  2014年   158篇
  2013年   169篇
  2012年   223篇
  2011年   214篇
  2010年   141篇
  2009年   99篇
  2008年   154篇
  2007年   151篇
  2006年   116篇
  2005年   114篇
  2004年   110篇
  2003年   78篇
  2002年   72篇
  2001年   8篇
  2000年   13篇
  1999年   18篇
  1998年   19篇
  1997年   17篇
  1996年   12篇
  1995年   9篇
  1994年   6篇
  1993年   10篇
  1992年   8篇
  1991年   5篇
  1990年   5篇
  1989年   6篇
  1988年   6篇
  1987年   3篇
  1986年   1篇
  1985年   5篇
  1984年   3篇
  1983年   3篇
  1982年   1篇
  1981年   6篇
  1980年   2篇
  1978年   1篇
  1977年   3篇
  1972年   2篇
  1969年   1篇
  1909年   1篇
排序方式: 共有2506条查询结果,搜索用时 0 毫秒
51.
Franciscanas Pontoporia blainvillei are small dolphins endemic to Brazil, Uruguay and Argentina. During routine pathologic examinations, chronic pneumonia associated with cholesterol deposits was found in 16.7% of stranded and incidentally bycaught franciscanas (n = 60), and was more frequent in dolphins from the Brazilian state of S?o Paulo (Franciscana Management Area II) and frequently accompanied by splenic lymphoid hyperplasia. It is unclear why these otherwise uncommon lesions were relatively frequent in the studied dolphins, and further research is advised.  相似文献   
52.
We previously described an escape mechanism exploited by Mycobacterium tuberculosis (Mtb) to prevent the generation of fully competent dendritic cells (DC). We have now tested the effect of isolated mycobacterial components on human monocyte differentiation into DC and demonstrated that cell wall (CW)-associated alpha-glucan induces monocytes to differentiate into DC (Glu-MoDC) with the same altered phenotype and functional behaviour of DC derived from Mtb-infected monocytes (Mt-MoDC). In fact, Glu-MoDC lack CD1 molecule expression, fail to upregulate CD80 and produce IL-10 but not IL-12. We also showed that Glu-MoDC are not able to prime effector T cells or present lipid antigens to CD1-restricted T-cell clones. Thus, we propose a mechanism of Mtb-monocyte interaction mediated by CW-associated alpha-glucan, which allows the bacterium to evade both innate and acquired immune responses.  相似文献   
53.
Proper assembly and maintenance of epithelia are critical for normal development and homeostasis. Here, using the Drosophila ovary as a model, we identify a role for the B1 isoform of the ecdysone receptor (EcR-B1) in this process. We performed a reverse genetic analysis of EcR-B1 function during oogenesis and demonstrate that silencing of this receptor isoform causes loss of integrity and multilayering of the follicular epithelium. We show that multilayered follicle cells lack proper cell polarity with altered distribution of apical and basolateral cell polarity markers including atypical-protein kinase C (aPKC), Discs-large (Dlg), and Scribble (Scrib) and aberrant accumulation of adherens junctions and F-actin cytoskeleton. We find that the EcR-B1 isoform is required for proper follicle cell polarity both during early stages of oogenesis, when follicle cells undergo the mitotic cell cycle, and at midoogenesis when these cells stop dividing and undergo several endocycles. In addition, we show that the EcR-B1 isoform is required during early oogenesis for follicle cell survival and that disruption of its function causes apoptotic cell death induced by caspase.  相似文献   
54.
Communication is an important aspect of human life, allowing us to powerfully coordinate our behaviour with that of others. Boiled down to its mere essentials, communication entails transferring a mental content from one brain to another. Spoken language obviously plays an important role in communication between human individuals. Manual gestures however often aid the semantic interpretation of the spoken message, and gestures may have played a central role in the earlier evolution of communication. Here we used the social game of charades to investigate the neural basis of gestural communication by having participants produce and interpret meaningful gestures while their brain activity was measured using functional magnetic resonance imaging. While participants decoded observed gestures, the putative mirror neuron system (pMNS: premotor, parietal and posterior mid-temporal cortex), associated with motor simulation, and the temporo-parietal junction (TPJ), associated with mentalizing and agency attribution, were significantly recruited. Of these areas only the pMNS was recruited during the production of gestures. This suggests that gestural communication relies on a combination of simulation and, during decoding, mentalizing/agency attribution brain areas. Comparing the decoding of gestures with a condition in which participants viewed the same gestures with an instruction not to interpret the gestures showed that although parts of the pMNS responded more strongly during active decoding, most of the pMNS and the TPJ did not show such significant task effects. This suggests that the mere observation of gestures recruits most of the system involved in voluntary interpretation.  相似文献   
55.
Heterocyst-forming cyanobacteria are important players at both evolutionary and ecological scales, but to date it has been difficult to establish their phylogenetic affiliations. We present data from a phylogenetic and molecular clock analysis of heterocystous cyanobacteria within the family Rivulariaceae, including the genera Calothrix, Rivularia, Gloeotrichia and Tolypothrix. The strains were isolated from distant geographic regions including fresh and brackish water bodies, microbial mats from beach rock, microbialites, pebble beaches, plus PCC strains 7103 and 7504. Phylogenetic inferences (distance, likelihood and Bayesian) suggested the monophyly of genera Calothrix and Rivularia. Molecular clock estimates indicate that Calothrix and Rivularia originated ~1500 million years ago (MYA) ago and species date back to 400-300 MYA while Tolypothrix and Gloeotrichia are younger genera (600-400 MYA).  相似文献   
56.
The effects of avilamycin, zinc bacitracin, and flavophospholipol on broiler gut microbial community colonization and bird performance in the first 17 days posthatch were investigated. Significant differences in gut microbiota associated with gut section, dietary treatment, and age were identified by terminal restriction fragment length polymorphism (T-RFLP), although no performance-related differences between dietary treatments were detected. Similar age-related shifts in the gut microbiota were identified regardless of diet but varied between the ilea and ceca. Interbird variabilities in ileal bacterial communities were reduced (3 to 7 days posthatch) in chicks fed with feed containing antimicrobial agents. Avilamycin and flavophospholipol had the most consistent effect on gut microbial communities. Operational taxonomic units (OTU) linked to changes in gut microbiota in birds on antimicrobial-supplemented diets were characterized and identified. Some OTUs could be identified to the species level; however, the majority could be only tentatively classified to the genus, family, order, or domain level. OTUs 140 to 146 (Lachnospiraceae), OTU 186/188 (Lactobacillus johnsonii), OTU 220 (Lachnospiraceae), OTUs 284 to 288 (unclassified bacterial spp. or Ruminococcaceae), OTU 296/298 (unclassified bacterium or Clostridiales), and OTU 480/482 (Oxalobacteraceae) were less prevalent in the guts of chicks fed antimicrobial-supplemented diets. OTU 178/180 (Lactobacillus crispatus), OTU 152 (Lactobacillus reuteri or unclassified Clostridiales), OTU 198/200 (Subdoligranulum spp.), and OTU 490/492 (unclassified bacterium or Enterobacteriaceae) were less prevalent in the gut of chicks raised on the antimicrobial-free diet. The identification of key bacterial species influenced by antimicrobial-supplemented feed immediately posthatch may assist in the formulation of diets that facilitate beneficial gut microbial colonization and, hence, the development of alternatives to current antimicrobial agents in feed for sustainable poultry production.  相似文献   
57.
Metabolomics embraces several strategies that aim to quantify cell metabolites in order to increase our understanding of how metabolite levels and interactions influence phenotypes. Metabolic footprinting represents a niche within metabolomics, because it focuses on the analysis of extracellular metabolites. Although metabolic footprinting represents only a fraction of the entire metabolome, it provides important information for functional genomics and strain characterization, and it can also provide scientists with a key understanding of cell communication mechanisms, metabolic engineering and industrial biotechnological processes. Due to the tight and convoluted relationship between intracellular metabolism and metabolic footprinting, metabolic footprinting can provide precious information about the intracellular metabolic status. Hereby, we state that integrative information from metabolic footprinting can assist in further interpretation of metabolic networks.  相似文献   
58.
59.
The highly conserved Tor kinases (TOR) and the protein kinase A (PKA) pathway regulate cell proliferation in response to growth factors and/or nutrients. In Saccharomyces cerevisiae, loss of either TOR or PKA causes cells to arrest growth early in G(1) and to enter G(0) by mechanisms that are poorly understood. Here we demonstrate that the protein kinase Rim15 is required for entry into G(0) following inactivation of TOR and/or PKA. Induction of Rim15-dependent G(0) traits requires two discrete processes, i.e., nuclear accumulation of Rim15, which is negatively regulated both by a Sit4-independent TOR effector branch and the protein kinase B (PKB/Akt) homolog Sch9, and release from PKA-mediated inhibition of its protein kinase activity. Thus, Rim15 integrates signals from at least three nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control entry into G(0), a key developmental process in eukaryotic cells.  相似文献   
60.
The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response.  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