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   1217篇
  免费   70篇
  国内免费   3篇
  1290篇
  2023年   6篇
  2022年   17篇
  2021年   22篇
  2020年   20篇
  2019年   27篇
  2018年   36篇
  2017年   29篇
  2016年   29篇
  2015年   46篇
  2014年   53篇
  2013年   53篇
  2012年   87篇
  2011年   94篇
  2010年   44篇
  2009年   56篇
  2008年   53篇
  2007年   64篇
  2006年   53篇
  2005年   63篇
  2004年   60篇
  2003年   41篇
  2002年   53篇
  2001年   22篇
  2000年   16篇
  1999年   25篇
  1998年   9篇
  1997年   7篇
  1996年   4篇
  1995年   3篇
  1993年   3篇
  1992年   24篇
  1991年   24篇
  1990年   21篇
  1989年   11篇
  1988年   10篇
  1987年   12篇
  1986年   12篇
  1985年   12篇
  1984年   9篇
  1983年   5篇
  1982年   4篇
  1979年   6篇
  1978年   7篇
  1977年   7篇
  1975年   3篇
  1971年   4篇
  1970年   3篇
  1969年   2篇
  1968年   2篇
  1967年   3篇
排序方式: 共有1290条查询结果,搜索用时 0 毫秒
61.
Journal of Physiology and Biochemistry - Many deleterious consequences for health of excessive fat accumulation are due to visceral fat. Browning of visceral fat is mainly cold dependent and has...  相似文献   
62.
63.
64.
Biological properties of the known Delta Sleep-Inducing Peptide (DSIP, WAGGDASGE) were studied in vivo in comparison with those of a new DSIP-homologous peptide (WKGGNASGE — ([K 2, N 5]DSIP, KND). This new peptide was recently discovered as the 324–332 fragment of the human lysine-specific histone demethylase 3B (EC 1.14.11, Swiss-Prot: Q7LBC6.1, 1761 a.a.) in the course of a computer search in available databases of proteins and nucleic acids. This demethylase belongs to the JmjC-domain-containing family of histone demethylases which are encoded by the JMJD1B gene and present in tissues of various mammals. These studies confirmed our preliminary conclusions on the functional similarity between the biological activities of DSIP and KND. The examined antioxidative, anticonvulsive, and behavioral effects of KND proved to be more pronounced than those of DSIP. The obtained results additionally sup-ported our hypothesis about KND being an endogenous prototype of a “real” DSIP.  相似文献   
65.
Inflammation plays an important role in vessel wall remodeling that occurs in atherosclerosis and postangioplasty restenosis. Monocytic chemoattractant protein-1 (MCP-1) is one of the main attractors of monocytes and some lymphocyte subsets to the damaged vessel. The aims of the study were to confirm MCP-1 participation in the development of acute coronary syndromes, to produce the potential MCP-1 peptide antagonist, and to investigate its effects in vitro and in vivo in different animal models of inflammation. MCP-1 plasma concentration was measured by ELISA (enzyme-linked immunosorbent assay). Chemokine receptor expression by cells isolated from human atherosclerotic lesions was assessed by direct immunofluorescence and flow cytometry. MCP-1 sequence was analyzed with Peptide Companion software and peptides were synthesized using Fmoc strategy. The peptide resistance to degradation was checked by 1H-NMR spectroscopy. The peptide effect on MCP-1-stimulated cell migration was studied in Boyden chamber and in mouse air pouch model, and its influence on lipopolysaccharide (LPS)-induced inflammatory cell recruitment was investigated in models of subcutaneous inflammation in rats and nonhuman primates. We revealed nearly a 2-fold increase of MCP-1 plasma level in patients with unstable angina in comparison with patients with stable angina. The atherosclerotic plaque specimens obtained from patients with unstable angina contained a significant amount of chemokine receptor-expressing leukocytes. Peptide from MCP-1 C-terminal 65-76 sequence (peptide X) inhibited MCP-1-stimulated monocytic cell migration in vitro and in vivo. Peptide X labeled with 99mTc accumulated specifically at sites of inflammation in rats. Peptide X administrated i.m and i.v. suppressed monocyte and granulocyte recruitment induced by subcutaneous injection of LPS in the back of rats and non-human primates. Our data demonstrate that MCP-1-mediated chemotaxis could be responsible for atherosclerotic plaque "destabilization". Peptide X may represent a new class of anti-inflammatory drugs to be used in cardiology.  相似文献   
66.
Linkage region between core and the O-chain of the lipopolysaccharide from Bordetella hinzii has been analyzed by NMR and MS analysis of the products, obtained by anhydrous HF treatment or consecutive ammonia and AcOH treatment of the LPS. The following structure of this region was deduced from the experimental results: [structure: see text] This structure is identical to the structure of the respective region of Bordetella parapertussis LPS. Polysaccharide part (PS) consists of not more than 15 2,3-diacetamido-2,3-dideoxyhexuronamides, methylated at the only hydroxyl group of the non-reducing terminal monosaccharide.  相似文献   
67.
In order to investigate any effect of truncated mutant huntingtin (tNhtt) aggregation on protein kinase C (PKC) signaling in Huntington's disease (HD), we studied a possible association of PKC isoforms with the aggregates using cellular and transgenic models of HD. In this report we describe an association of mutant tNhtt with at least three PKC isoforms (alpha, delta, zeta), as revealed by co-immunoprecipitation assays and immunocytochemistry in a cellular model of HD (Neuro2a cells expressing tNhtt-150Q-EGFP), as well as a specific association of PKC delta with intranuclear aggregates in a transgenic model (R6/2 mice). Immunoblot analysis of isolated nuclear fractions shows an elevation of nuclear PKC delta in transgenic brain tissue. The observed elevation has a strong similarity with the apoptotic translocation of PKC delta detected in experiments with the mouse neuroblastoma Neuro2a cells. Using a Neuro2a cell line expressing tNhtt with the nuclear localization signal, we demonstrate the association of PKC delta with intranuclear aggregates and present evidence that accumulation of PKC delta in cell nuclei does not depend on mutant htt nuclear translocation. Our results suggest that the association of PKC delta with intranuclear htt-aggregates may affect its apoptotic function in a transgenic model of HD.  相似文献   
68.

Background

Speciose clades usually harbor species with a broad spectrum of adaptive strategies and complex distribution patterns, and thus constitute ideal systems to disentangle biotic and abiotic causes underlying species diversification. The delimitation of such study systems to test evolutionary hypotheses is difficult because they often rely on artificial genus concepts as starting points. One of the most prominent examples is the bellflower genus Campanula with some 420 species, but up to 600 species when including all lineages to which Campanula is paraphyletic. We generated a large alignment of petD group II intron sequences to include more than 70% of described species as a reference. By comparison with partial data sets we could then assess the impact of selective taxon sampling strategies on phylogenetic reconstruction and subsequent evolutionary conclusions.

Methodology/Principal Findings

Phylogenetic analyses based on maximum parsimony (PAUP, PRAP), Bayesian inference (MrBayes), and maximum likelihood (RAxML) were first carried out on the large reference data set (D680). Parameters including tree topology, branch support, and age estimates, were then compared to those obtained from smaller data sets resulting from “classification-guided” (D088) and “phylogeny-guided sampling” (D101). Analyses of D088 failed to fully recover the phylogenetic diversity in Campanula, whereas D101 inferred significantly different branch support and age estimates.

Conclusions/Significance

A short genomic region with high phylogenetic utility allowed us to easily generate a comprehensive phylogenetic framework for the speciose Campanula clade. Our approach recovered 17 well-supported and circumscribed sub-lineages. Knowing these will be instrumental for developing more specific evolutionary hypotheses and guide future research, we highlight the predictive value of a mass taxon-sampling strategy as a first essential step towards illuminating the detailed evolutionary history of diverse clades.  相似文献   
69.
One hundred eighty nine children with acute bronchopulmonary infectious pathological processes were examined bacteriologically and serologically for typical pneumotropic pathogens, 47 of them being as well examined for atypical organisms. Microbial associations mainly with Mycoplasma and Pneumocystis and to a lesser extent with Chlamydia were isolated from the majority of the children. Reactivation of the cytomegalovirus infection was observed in 25 per cent of the children. Pneumonia and bronchitis due to Mycoplasma pneumoniae either as a monoagent or in associations were mainly stated in children over 7 years of age. No significant changes between the indices of the infection due to a definite organism and the active progression of the infectious process of the same etiology were revealed, though in the cases of chlamydiosis the changes reached almost 10 per cent. In cases of acute bronchitis and pneumonia the chlamydial or cytomegalovirus infection could be assumed to be of the persisting nature, mainly acute in cases of pneumococcal infection, mixed in cases of hemophilic or pneumocystic infection, primary contamination with a tendency to prolonged in cases of mycoplasmic infection. The findings of the examination and the clinical and anamnestic data showed that the clinical picture of acute pneumonia had specific features associated with the supposed etiological agents, still it could change under the action of associations of pneumotropic pathogens.  相似文献   
70.
Hydrobiologia - Marine ecosystems on continental shelves face multiple challenges due to anthropogenic disturbances, many of which can change the seawater stoichiometry (C:N:P) and consequently...  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