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   6259篇
  免费   329篇
  国内免费   10篇
  6598篇
  2024年   19篇
  2023年   92篇
  2022年   224篇
  2021年   334篇
  2020年   158篇
  2019年   178篇
  2018年   192篇
  2017年   160篇
  2016年   288篇
  2015年   315篇
  2014年   338篇
  2013年   501篇
  2012年   448篇
  2011年   491篇
  2010年   275篇
  2009年   253篇
  2008年   329篇
  2007年   308篇
  2006年   279篇
  2005年   231篇
  2004年   211篇
  2003年   178篇
  2002年   174篇
  2001年   50篇
  2000年   41篇
  1999年   40篇
  1998年   32篇
  1997年   32篇
  1996年   18篇
  1995年   27篇
  1994年   29篇
  1993年   22篇
  1992年   19篇
  1991年   16篇
  1990年   15篇
  1989年   18篇
  1988年   18篇
  1987年   18篇
  1986年   8篇
  1985年   23篇
  1984年   21篇
  1983年   16篇
  1982年   27篇
  1981年   14篇
  1980年   18篇
  1979年   11篇
  1978年   13篇
  1977年   11篇
  1974年   8篇
  1966年   7篇
排序方式: 共有6598条查询结果,搜索用时 15 毫秒
101.
Abscess formation associated with intra-abdominal sepsis causes severe morbidity and can be fatal. Previous studies have implicated T cells in the pathogenesis of abscess formation, and we have recently shown that CD4(+) T cells activated in vitro by zwitterionic capsular polysaccharides from abscess-inducing bacteria such as Staphylococcus aureus and Bacteroides fragilis initiate this host response when transferred to naive rats. In this study, we show that mice deficient in alphabetaTCR-bearing T cells or CD4(+) T cells fail to develop abscesses following challenge with B. fragilis or abscess-inducing zwitterionic polysaccharides, compared with CD8(-/-) or wild-type animals. Transfer of CD4(+) T cells from wild-type mice to alphabetaTCR(-/-) animals reconstituted this ability. The induction of abscesses required T cell costimulation via the CD28-B7 pathway, and T cell transfer experiments with STAT4(-/-) and STAT6(-/-) mice demonstrated that this host response is dependent on STAT4 signaling. Significantly higher levels of IL-17, a proinflammatory cytokine produced almost exclusively by activated CD4(+) T cells, were associated with abscess formation in Th2-impaired (STAT6(-/-)) mice, while STAT4(-/-) mice had significantly lower levels of this cytokine than control animals. The formation of abscesses was preceded by an increase in the number of activated CD4(+) T cells in the peritoneal cavity 24 h following bacterial challenge. Confocal laser-scanning microscopy analysis revealed that CD4(+) T cells comprise the abscess wall in these animals and produce IL-17 at this site. Administration of a neutralizing Ab specific for IL-17 prevented abscess formation following bacterial challenge in mice. These data delineate the specific T cell response necessary for the development of intra-abdominal abscesses and underscore the role of IL-17 in this disease process.  相似文献   
102.
Oxidative stress, induced by various neurodegenerative diseases, initiates a cascade of events leading to apoptosis, and thus plays a critical role in neuronal injury. In this study, we have investigated the potential neuroprotective effect of the octadecaneuropeptide (ODN) on 6‐hydroxydopamine (6‐OHDA)‐induced oxidative stress and apoptosis in cerebellar granule neurons (CGN). ODN, which is produced by astrocytes, is an endogenous ligand for both central‐type benzodiazepine receptors (CBR) and a metabotropic receptor. Incubation of neurons with subnanomolar concentrations of ODN (10?18 to 10?12 M) inhibited 6‐OHDA‐evoked cell death in a concentration‐dependent manner. The effect of ODN on neuronal survival was abrogated by the metabotropic receptor antagonist, cyclo1–8[DLeu5]OP, but not by a CBR antagonist. ODN stimulated polyphosphoinositide turnover and ERK phosphorylation in CGN. The protective effect of ODN against 6‐OHDA toxicity involved the phospholipase C/ERK MAPK transduction cascade. 6‐OHDA treatment induced an accumulation of reactive oxygen species, an increase of the expression of the pro‐apoptotic gene Bax, a drop of the mitochondrial membrane potential and a stimulation of caspase‐3 activity. Exposure of 6‐OHDA‐treated cells to ODN blocked all the deleterious effects of the toxin. Taken together, these data demonstrate for the first time that ODN is a neuroprotective agent that prevents 6‐OHDA‐induced oxidative stress and apoptotic cell death.  相似文献   
103.
The contribution of soil seed bank of a desert endemic plant species in maintaining genetic diversity has been addressed in this paper through investigating the differences in genetic diversity and structure (using AFLP markers) between plants grown from soil seed bank and standing crop plants within and among five populations of H. sinaicum growing at St. Katherine Protectorate, southern Sinai, Egypt. Standard genetic diversity measures showed that the molecular variation within and among populations was highly significantly different between standing crop and soil seed bank. While soil seed bank had lower genetic diversity than standing crop populations, pooling soil seed bank with standing crop samples resulted in higher diversity. The results revealed also that soil seed bank had lower differentiation (7 %) than among populations of the standing crop (18 %). Results of neighbor-joining, Bayesian clustering and principal coordinate analysis showed that soil seed banks had a separate gene pool different from standing crop. The study came to the conclusion that the genetic variation of the soil seed bank contributes significantly to the genetic variation of the species. This also stresses the importance of elucidating the genetic diversity and structure of the soil seed bank for any sound and long-term conservation efforts for desert species. These have been growing in small-size populations for a long time that any estimates gained only from aboveground sampling of populations may be ambiguous.  相似文献   
104.
Summary Bacteria utilizing high concentrations of acetonitrile as the sole carbon source were isolated and identified asChromobacterium sp. andPseudomonas aeruginosa. Maximum growth was attained after 96 h of incubation andP. aeruginosa grew slightly faster thanChromobacterium sp. The strains were able to grow and oxidize acetonitrile at concentrations as high as 600 mM. However, higher concentrations inhibited growth and oxygen uptake. Degradation studies with (14C)acetonitrile indicated 57% of acetonitrile was degraded byPseudomonas aeruginosa as compared to 43% byChromobacterium. The isolates utilized different nitrile compounds as carbon substrates.  相似文献   
105.
2',3'-Dideoxy-3'-C-methyl nucleosides bearing the five naturally occurring nucleic acid bases were synthesized. Additionally, the 3'-deoxy-3'-C-methyl nucleoside analogues bearing 5-aminoimidazole-4-carboxamide as well as 1,2,4-triazole-3-carboxamide moieties were prepared. The synthesis of the corresponding 2',3'-dideoxy-3'-C-methyl triazole derivative was also accomplished. The dideoxynucleoside derivatives were prepared by radical deoxygenation from their 3'-deoxy-3'-C-methyl parent ribonucleosides. When evaluated for their antiviral activity in cell culture experiments, none of these compounds showed any significant antiviral activity.  相似文献   
106.

Matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9) are involved in the breakdown of extracellular matrix in normal physiological processes as well as in disease processes, such as cancer metastasis. We conducted this work to study the role of MMP-2 and MMP-9 in breast cancer by measuring their plasma concentrations before and after surgery. Also, to examine if their levels can reflect the stage of disease and prognosis. Forty-eight breast cancer patients and 13 patients with benign breast diseases were included in the study. MMP-2 and MMP-9 levels were measured by ELISA and semi-quantitative real-time PCR. MMP-2 and MMP-9 levels in plasma were determined by ELISA immediately before surgery and during 6 to 12 months after curative surgery. We observed a significant increase in the level of MMP-9 mRNA expression in breast cancer patients in comparison to their normal breast tissues and to tissues of benign breast disease. In all TNM tumor stages, the plasma levels of MMP-2 and MMP-9 were increased significantly before curative surgery in the studied patients with breast carcinoma and decreased significantly after surgery. Both MMP-2 and MMP-9 may be used as a possible marker for follow-up or as a marker that reflects the response of the disease to treatment.

  相似文献   
107.
Molecular Biology Reports - H2O2 generated during the oxidative burst, plays important roles in plant defenses responses against pathogens. In this study we examined the role of H2O2 on bacterial...  相似文献   
108.

In this study we tested the hypotheses that root classes would exhibit distinctive anatomical and architectural responses to drought stress, and that those responses would vary along the root axes. The root systems of four maize (Zea mays L.) sweet corn genotypes designated SC1, SC2, SC3 and SC4 were phenotyped under well-watered and drought treatments in greenhouse mesocosms, permitting increasing stratification of moisture availability as the drought progressed. Anatomical and architectural responses to drought were evaluated for each root class. Lignin distribution was assessed by image processing of UV-illuminated root cross-sections acquired by laser ablation tomography. The two cultivars with less biomass reduction under drought, SC3 and SC4, substantially enhanced lateral root development along the apical segments of axial roots when plants were grown with drought stress. These segments grew into the deeper part of the mesocosm where more moisture was available. Apical segments of the axial and large lateral roots from drought-stressed plants were thicker and had greater theoretical axial water conductance than basal segments, especially in SC3 and SC4. Basal segments of crown roots of SC3 and SC4 showed increased lignification of the stele under drought. Root anatomical and architectural responses to drought are complex and vary among cultivars and root classes, and along root axes. Drought-induced proliferation of lateral roots on apical segments of axial roots would be expected to enhance deep water acquisition, while lignification of axial roots could help preserve axial water transport.

  相似文献   
109.
The diets of the most conspicuous reef‐fish species from northern Patagonia, the carnivorous species Pseudopercis semifasciata, Acanthistius patachonicus, Pinguipes brasilianus and Sebastes oculatus were studied. Pinguipes brasilianus had the narrowest diet and most specialized feeding strategy, preying mostly on reef‐dwelling organisms such as sea urchins, limpets, bivalves, crabs and polychaetes. The diet of A. patachonicus was characterized by the presence of reef and soft‐bottom benthic organisms, mainly polychaetes, crabs and fishes. Pseudopercis semifasciata showed the broadest spectrum of prey items, preying upon reef, soft‐bottom and transient organism (mainly fishes, cephalopods and crabs). All S. oculatus guts were empty, but stable‐isotope analyses suggested that this species consumed small fishes and crabs. In general, P. brasilianus depended on local prey populations and ate different reef‐dwelling prey than the other species. Pseudopercis semifasciata, A. patachonicus and probably S. oculatus, however, had overlapping trophic niches and consumed resources from adjacent environments. The latter probably reduces the importance of food as a limiting resource for these reef‐fish populations, facilitating their coexistence in spite of their high trophic overlap.  相似文献   
110.
The ovarian function is controlled by endocrine factors and neural influence. In late pregnant rat, androstenedione, from the coeliac ganglion, has a luteotrophic effect in the ex vivo coeliac ganglion-superior ovarian nerve-ovary system. In this work we investigate the presence of androgen receptors in the coeliac ganglion of late pregnant rats by immunohistochemistry. We also explore, from a physiological point of view, the potential participation of these receptors in the androstenedione ganglionic action on progesterone release and metabolism, as well as on nitrites release in the ovary compartment. The coeliac ganglion was isolated after being fixed in situ and immunohistochemistry was performed. In the system, three experimental groups were used with the addition of (a) androstenedione, (b) flutamide, and (c) androstenedione plus flutamide in the ganglion compartment. Progesterone and nitrite concentrations were determined in the ovary compartment at different incubation times. Corpora lutea samples isolated at the end of incubation were used to determine the expressions and activities of the progesterone synthesis (3β-hydroxysteroid-dehydrogenase, 3β-HSD) and degradation (20α-hydroxysteroid-dehydrogenase, 20α-HSD) enzymes. Immunohistochemistry revealed cytoplasmatic androgen receptor immunoreactivity in neural somas in the coeliac ganglion. In the coeliac ganglion-superior ovarian nerve-ovary system, androstenedione addition increased 3β-HSD and decreased 20α-HSD, showed a tendency to decrease 20α-HSD expression, and increased nitrites release in relation to control. Androstenedione plus flutamide decreased progesterone and nitrites release in relation to the androstenedione group. This work demonstrates the presence of androgen receptors in neurons of celiac ganglion and provides evidence for the luteotrophic action of androstenedione via a neural pathway that may be mediated by these receptors.  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