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   5390篇
  免费   355篇
  5745篇
  2024年   4篇
  2023年   20篇
  2022年   72篇
  2021年   100篇
  2020年   49篇
  2019年   81篇
  2018年   116篇
  2017年   95篇
  2016年   155篇
  2015年   223篇
  2014年   276篇
  2013年   416篇
  2012年   457篇
  2011年   444篇
  2010年   277篇
  2009年   207篇
  2008年   344篇
  2007年   344篇
  2006年   324篇
  2005年   322篇
  2004年   283篇
  2003年   233篇
  2002年   247篇
  2001年   53篇
  2000年   47篇
  1999年   55篇
  1998年   50篇
  1997年   37篇
  1996年   43篇
  1995年   40篇
  1994年   31篇
  1993年   43篇
  1992年   28篇
  1991年   16篇
  1990年   17篇
  1989年   16篇
  1988年   16篇
  1987年   16篇
  1986年   16篇
  1985年   13篇
  1984年   22篇
  1983年   17篇
  1982年   6篇
  1981年   15篇
  1980年   9篇
  1979年   8篇
  1978年   6篇
  1977年   7篇
  1976年   8篇
  1965年   3篇
排序方式: 共有5745条查询结果,搜索用时 11 毫秒
81.
82.
83.

Background  

Lung function is a strong predictor of cardiovascular and all-cause mortality. Previous studies suggest that alcohol exposure may be linked to impaired pulmonary function through oxidant-antioxidant mechanisms. Alcohol may be an important source of oxidants; however, wine contains several antioxidants. In this study we analyzed the relation of beverage specific alcohol intake with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in a random sample of 1555 residents of Western New York, USA.  相似文献   
84.
Chagas’ disease is caused by Trypanosoma cruzi, a protozoan transmitted to humans by blood-feeding insects, blood transfusion or congenitally. Previous research led us to discover a parasite proline racemase (TcPRAC) and to establish its validity as a target for the design of new chemotherapies against the disease, including its chronic form. A known inhibitor of proline racemases, 2-pyrrolecarboxylic acid (PYC), is water-insoluble. We synthesized soluble pyrazole derivatives, but they proved weak or inactive TcPRAC inhibitors. TcPRAC catalytic site is too small and constrained when bound to PYC to allow efficient search for new inhibitors by virtual screening. Forty-nine intermediate conformations between the opened enzyme structure and the closed liganded one were built by calculating a transition path with a method we developed. A wider range of chemical compounds could dock in the partially opened intermediate active site models in silico. Four models were selected for known substrates and weak inhibitors could dock in them and were used to screen chemical libraries. Two identified soluble compounds, (E)-4-oxopent-2-enoic acid (OxoPA) and its derivative (E)-5-bromo-4-oxopent-2-enoic acid (Br-OxoPA), are irreversible competitive inhibitors that presented stronger activity than PYC on TcPRAC. We show here that increasing doses of OxoPA and Br-OxoPA hamper T. cruzi intracellular differentiation and fate in mammalian host cells. Our data confirm that through to their binding mode, these molecules are interesting and promising as lead compounds for the development of chemotherapies against diseases where active proline racemases play essential roles.  相似文献   
85.
In this article we present evidence for a relationship between chromosome gene loci and the topological properties of the protein-protein interaction network corresponding to the set of genes under consideration. Specifically, for each chromosome of the Saccharomyces cerevisiae genome, the distribution of the intra-chromosome inter-gene distances was analyzed and a positive correlation with the distance among the corresponding proteins of the protein-protein interaction network was found. In order to study this relationship we used concepts based on non-parametric statistics and information theory.We provide statistical evidence that if two genes are closely located, then it is likely that their protein products are closely located in the protein-protein interaction network, or in other words, that they are involved in the same biological process.  相似文献   
86.
87.
The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or telomere-related SNPs. A total of 796 cases and 770 controls were genotyped for 517 SNPs in 39 telomere-related genes genotyped with a custom-made array. Replication of the top SNPs was conducted in two American populations consisting of 488 subjects from 53 melanoma-prone families and 1,086 cases and 1,024 controls from a case-control study. We estimated odds ratios for associations with SNPs and combined SNP P-values to compute gene region-specific, functional group-specific, and overall P-value using an adaptive rank-truncated product algorithm. In the Mediterranean population, we found suggestive evidence that RECQL4, a gene involved in genome stability, RTEL1, a gene regulating telomere elongation, and TERF2, a gene implicated in the protection of telomeres, were associated with melanoma, the presence of dysplastic nevi and number of nevi, respectively. However, these associations were not found in the American samples, suggesting variable melanoma susceptibility for these genes across populations or chance findings in our discovery sample. Larger studies across different populations are necessary to clarify these associations.  相似文献   
88.
Testicular weight and DNA content were markedly reduced (63 and 69%) in weanling Long-Evans rat pups rendered hypothyroid from birth by administration of propylthiouracil (PTU), a reversible goitrogen. These growth deficits worsened to >80% by continuing hypothyroidism beyond weaning, to days 50 and 90. Recovery of thyroid function, brought about by discontinuing PTU at weaning, resulted in a paradoxical stimulation of testis growth, amounting to increased weight (40%), DNA content (60%) and size by 90 days, compared to age-matched controls. In the 25-day or older hypothyroid rats, testicular structure was immature and spermatogenesis markedly delayed, as evident by closed lumen and significantly reduced diameter of seminiferous tubules (38%), thickness of germinal layer (70%), and number of primary spermatocytes (86%), compared to control. Hypothyroidism did not alter the number of tubules per testis cross section. In the 90-day recovery rats, numbers of seminiferous tubules were unchanged but tubular diameter was significantly (20%) larger than in controls and spermatogenesis appeared very active as indicated by significantly increased germinal layer thickness (22%) and total number and density of primary spermatocytes (55% and 40%). The results show that although postnatal hypothyroidism is deleterious for testicular growth and spermatogenesis, recovery from this condition leads to enhanced seminiferous tubular growth and spermatogenesis.  相似文献   
89.
Summary Cl influx at the luminal border of the epithelium of rabbit gallbladder was measured by 45-sec exposures to36Cl and3H-sucrose (as extracellular marker). Its paracellular component was evaluated by the use of 25mm SCN which immediately and completely inhibits Cl entry into the cell. Cellular influx was equal to 16.7eq cm–2 hr–1 and decreased to 8.5eq cm–2 hr–1 upon removal of HCO 3 from the bathing media and by bubbling 100% O2 for 45 min. When HCO 3 was present, cellular influx was again about halved by the action of 10–4 m acetazolamide, 10–5 to 10–4 m furosemide, 10–5 to 10–4 m 4-acetamido-4-isothiocyanostilbene-2,2-disulfonate (SITS), 10–3 m amiloride. The effects of furosemide and SITS were tested at different concentrations of the inhibitor and with different exposure times: they were maximal at the concentrations reported above and nonadditive. In turn, the effects of amiloride and SITS were not additive. Acetazolamide reached its maximal action after an exposure of about 2 min. When exogenous HCO 3 was absent, the residual cellular influx was insensitive to acetazolamide, furosemide and SITS. When exogenous HCO 3 was present in the salines, Na+ removal from the mucosal side caused a slow decline of cellular Cl influx; conversely, it immediately abolished cellular Cl influx in the absence of HCO 3 . In conclusion, about 50% of cellular influx is sensitive to HCO 3 , inhibitable by SCN, acetazolamide, furosemide, SITS and amiloride and furthermore slowly dependent on Na+. The residual cellular influx is insensitive to bicarbonate, inhibitable by SCN, resistant to acetazolamide, furosemide, SITS and amiloride, and immediately dependent on Na+. Thus, about 50% of apical membrane NaCl influx appears to result from a Na+/H+ and Cl/HCO 3 exchange, whereas the residual influx seems to be due to Na+–Cl contranport on a single carrier. Whether both components are simultaneously present or the latter represents a cellular homeostatic counterreaction to the inhibition of the former is not clear.  相似文献   
90.
Site-specific integration and excision of pMEA100 in Nocardia mediterranei   总被引:5,自引:0,他引:5  
Summary Nocardia mediterranei strain LBG A3136 contains the 23.7 kb element pMEA100 in a chromosomally integrated form as well as in the free state (Moretti et al. 1985). The integrated form of this element can be excised precisely from the Nocardia chromosome without any accompanying rearrangements in flanking chromosomal DNA. After transfer into plasmid-free mutant strains, pMEA100 reintegrates site specifically into its original chromosomal locus. The exact mapping of the pMEA100 integration site was accomplished by restriction analysis and DNA sequencing. The attachment site of pMEA100, the junctions of its integrated form and plasmid-free chromosomal DNA of N. mediterranei contain an identical 47 bp long sequence which is probably required for site-specific recombination connected with integration and excision of pMEA100. Only one such sequence was found in the chromosome of pMEA100-free N. mediterranei derivatives as suggested by the single integration locus.  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