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   4711篇
  免费   503篇
  国内免费   4篇
  5218篇
  2021年   76篇
  2019年   47篇
  2018年   71篇
  2017年   58篇
  2016年   102篇
  2015年   118篇
  2014年   163篇
  2013年   198篇
  2012年   250篇
  2011年   260篇
  2010年   199篇
  2009年   141篇
  2008年   272篇
  2007年   245篇
  2006年   182篇
  2005年   186篇
  2004年   186篇
  2003年   163篇
  2002年   169篇
  2001年   101篇
  2000年   85篇
  1999年   94篇
  1998年   68篇
  1997年   56篇
  1996年   57篇
  1995年   50篇
  1994年   42篇
  1993年   46篇
  1992年   81篇
  1991年   86篇
  1990年   69篇
  1989年   73篇
  1988年   88篇
  1987年   54篇
  1986年   60篇
  1985年   51篇
  1984年   59篇
  1983年   49篇
  1982年   36篇
  1981年   39篇
  1980年   49篇
  1979年   50篇
  1978年   49篇
  1976年   46篇
  1975年   35篇
  1974年   34篇
  1973年   42篇
  1972年   33篇
  1970年   34篇
  1969年   33篇
排序方式: 共有5218条查询结果,搜索用时 15 毫秒
51.
52.

Background  

Trichomonosis caused by Trichomonas vaginalis is the number one, non-viral sexually transmitted disease (STD) that affects more than 250 million people worldwide. Immunoglobulin A (IgA) has been implicated in resistance to mucosal infections by pathogens. No reports are available of IgA-reactive proteins and the role, if any, of this class of antibody in the control of this STD. The availability of an IgA monoclonal antibody (mAb) immunoreactive to trichomonads by whole cell (WC)-ELISA prompted us to characterize the IgA-reactive protein of T. vaginalis.  相似文献   
53.
Although issues related to the management of invasive alien species are receiving increasing attention, little is known about which factors affect the likelihood of success of management measures. We applied two data mining techniques, classification trees and boosted trees, to identify factors that relate to the success of management campaigns aimed at eradicating invasive alien invertebrates, plants and plant pathogens. We assembled a dataset of 173 different eradication campaigns against 94 species worldwide, about a half of which (50.9%) were successful. Eradications in man-made habitats, greenhouses in particular, were more likely to succeed than those in (semi-)natural habitats. In man-made habitats the probability of success was generally high in Australasia, while in Europe and the Americas it was higher for local infestations that are easier to deal with, and for international campaigns that are likely to profit from cross-border cooperation. In (semi-) natural habitats, eradication campaigns were more likely to succeed for plants introduced as an ornamental and escaped from cultivation prior to invasion. Averaging out all other factors in boosted trees, pathogens, bacteria and viruses were most, and fungi the least likely to be eradicated; for plants and invertebrates the probability was intermediate. Our analysis indicates that initiating the campaign before the extent of infestation reaches the critical threshold, starting to eradicate within the first four years since the problem has been noticed, paying special attention to species introduced by the cultivation pathway, and applying sanitary measures can substantially increase the probability of eradication success. Our investigations also revealed that information on socioeconomic factors, which are often considered to be crucial for eradication success, is rarely available, and thus their relative importance cannot be evaluated. Future campaigns should carefully document socioeconomic factors to enable tests of their importance.  相似文献   
54.
Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential.  相似文献   
55.
Estrogen Therapy (ET) may protect against age-related cognitive decline and neuropsychiatric disorders (e.g. Alzheimer's disease). The biological basis for this putative neuroprotective effect is not fully understood, but may include modulation of cholinergic systems. Cholinergic dysfunction has been implicated in age-related memory impairment and Alzheimer's disease. However, to date no one has investigated the effect of long-term ET on brain cholinergic muscarinic receptor aging, and related this to cognitive function. We used Single Photon Emission Tomography (SPET) and (R,R)[(123)I]-I-QNB, a novel ligand with high affinity for m(1)/m(4) muscarinic receptors, to examine the effect of long-term ET and age on brain m(1)/m(4) receptors in healthy females. We included 10 younger premenopausal subjects and 22 postmenopausal women; 11 long-term ET users (all treated following surgical menopause) and 11 ET never-users (surgical menopause, n=2). Also, verbal memory and executive function was assessed in all postmenopausal subjects. Compared to young women, postmenopausal women (ET users and never-users combined) had significantly lower muscarinic receptor density in all brain regions examined. ET users also had higher muscarinic receptor density than ET never-users in all the brain regions, and this reached statistical significance in left striatum and hippocampus, lateral frontal cortex and thalamus. Moreover, in ET users, (R,R)[(123)I]-I-QNB binding in left hippocampus and temporal cortex was significantly positively correlated with plasma estradiol levels. We also found evidence for improved executive function in ET users as compared to ET never-users. However, there was no significant relationship between receptor binding and cognitive function within any of the groups. In healthy postmenopausal women use of long-term ET is associated with reduced age-related differences in muscarinic receptor binding, and this may be related to serum estradiol levels.  相似文献   
56.
Preface     
  相似文献   
57.
Undomesticated strains of Bacillus subtilis exhibit extensive colony spreading on certain soft agarose media: first the formation of dendritic clusters of cells, followed by spreading (pellicle-like) growth to cover the entire surface. These phases of colonization are dependent on the level of potassium ion (K(+)) but independent of flagella, as verified with a mutant with a hag gene replacement; this latter finding highlights the importance of sliding motility in colony spreading. Exploring the K(+) requirement, directed mutagenesis of the higher-affinity K(+) transporter KtrAB, but not the lower-affinity transporter KtrCD, was found to inhibit surface colonization unless sufficient KCl was added. To identify other genes involved in K(+)-dependent colony spreading, transposon insertion mutants in wild-type strain 3610 were screened. Disruption of genes for pyrimidine (pyrB) or purine (purD, purF, purH, purL, purM) biosynthetic pathways abolished the K(+)-dependent spreading phase. Consistent with a requirement for functional nucleic acid biosynthesis, disruption of purine synthesis with the folic acid antagonist sulfamethoxazole also inhibited spreading. Other transposon insertions disrupted acetoin biosynthesis (the alsS gene), acidifying the growth medium, glutamine synthetase (the glnA gene), and two surfactin biosynthetic genes (srfAA, srfAB). This work identified four classes of surface colonization mutants with defective (i) potassium transport, (ii) surfactin formation, (iii) growth rate or yield, or (iv) pH control. Overall, the ability of B. subtilis to colonize surfaces by spreading is highly dependent on balanced nucleotide biosynthesis and nutrient assimilation, which require sufficient K(+) ions, as well as growth conditions that promote sliding motility.  相似文献   
58.
59.
B Mazumdar  K Meyer  R Ray 《PloS one》2012,7(8):e44461
Activated hepatic stellate cells (HSCs) are the major source for alteration of extracellular matrix in fibrosis and cirrhosis. Conditioned medium (CM) collected from immortalized human hepatocytes (IHH) have earlier been shown to be responsible for apoptosis of HSCs. In this study, we have shown that antibodies raised against a peptide derived from a linear B-cell epitope in the N-terminal region of gelsolin identified a gelsolin fragment in IHH CM. Analysis of activated stellate cell death by CM collected from Huh7 cells transfected with plasmids encoding gelsolin deletion mutants suggested that the N-terminal half of gelsolin contained sequences which were responsible for stellate cell death. Further analysis determined that this activity was restricted to a region encompassing amino acids 1-70 in the gelsolin sequence; antibody directed to an epitope within this region was able to neutralize stellate cell death. Gelsolin modulation of cell death using this fragment involved upregulation of TRAIL-R1 and TRAIL-R2, and involved caspase 3 activation by extrinsic pathway. The apoptotic activity of N-terminal gelsolin fragments was restricted to activated but not quiescent stellate cells indicating its potential application in therapeutic use as an anti-fibrotic agent. Gelsolin fragments encompassing N-terminal regions in polypeptides of different molecular sizes were detected by N-terminal peptide specific antiserum in IHH CM immunoprecipitated with chronically HCV infected patient sera, suggesting the presence of autoantibodies generated against N-terminal gelsolin fragments in patients with chronic liver disease.  相似文献   
60.
We have constructed a collection of canine–rodent microcell hybrid cell lines by fusion of canine fibroblast microcell donors with immortalized rodent recipient cells. Characterization of the hybrid cell lines using a combination of fluorescencein situhybridization and PCR analysis of canine microsatellite repeat sequences allowed selection of a panel of hybrids in which most canine chromosomes are represented. Approximately 90% of genetic markers and genes that were tested could be assigned to 1 of 31 anonymous canine chromosome groups, based on common patterns of retention in the hybrid set. Many of these putative chromosome groups have now been validated by linkage analysis. This panel of cell lines provides a tool for development of genetic, physical, and comparative maps of the canine genome.  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