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   1238篇
  免费   72篇
  2023年   2篇
  2022年   7篇
  2021年   14篇
  2020年   6篇
  2019年   10篇
  2018年   18篇
  2017年   17篇
  2016年   27篇
  2015年   32篇
  2014年   49篇
  2013年   92篇
  2012年   68篇
  2011年   84篇
  2010年   48篇
  2009年   49篇
  2008年   87篇
  2007年   98篇
  2006年   74篇
  2005年   69篇
  2004年   83篇
  2003年   82篇
  2002年   88篇
  2001年   11篇
  2000年   13篇
  1999年   22篇
  1998年   22篇
  1997年   16篇
  1996年   6篇
  1995年   13篇
  1994年   10篇
  1993年   14篇
  1992年   8篇
  1991年   11篇
  1990年   6篇
  1989年   3篇
  1988年   2篇
  1987年   4篇
  1986年   2篇
  1985年   4篇
  1984年   3篇
  1983年   4篇
  1982年   10篇
  1981年   4篇
  1978年   2篇
  1977年   3篇
  1974年   2篇
  1972年   3篇
  1963年   1篇
  1962年   1篇
  1961年   1篇
排序方式: 共有1310条查询结果,搜索用时 15 毫秒
941.
942.
943.
Successful somatic cloned animal production has been reported in various domesticated species, including cattle; however, it is associated with a high rate of pregnancy failure. The low cloning yield could possibly arise from either an abnormal and/or poorly developed placenta. In comparison to control cows, fewer placentomes were found in somatic cell nuclear recipient (NT) cows at day 60 of gestation, suggesting a retardation of fetal/placental growth in these animals. NT cows not only had fewer numbers of chorionic villi but also had poorly developed caruncles. Macroscopic examination revealed atypical development of the placentome in terms of shape and size. Histological disruption of chorionic villi and caruncular septum was found in NT cows. Of particular interest was that the expression of genes, as well as proteins in the placentome, was disparate between NT and artificially inseminated cows, especially placental lactogen (PL) and pregnancy-associated glycoprotein (PAG). In contrast, prolactin-related protein-1 (PRP-1) signals were comparable across cows, including NT cows carrying immotile fetuses. The expression of extracellular matrix degrading molecule, heparanase (HPA), in NT cows was divergent from that of control cows. Microarray data suggest that gene expression was disorientated in early stages of implantation in NT cows, but this was eliminated with progression of gestation. These findings strongly support a delay in trophoblast development during early stages of placentation in NT cows, and suggest that placental specific proteins, including PLs, PAGs, and HPA, are key indicators for the aberration of gestation and placental function in cows.  相似文献   
944.
The surface layer of archaeobacteria protects cells from extreme environments and, in Methanosarcina, may regulate cell adhesion. We identify three domain types that account for the complete architecture of numerous Methanosarcina surface layer proteins (SLPs). We solve the crystal structure for two of these domains, which correspond to the two N-terminal domains of an M. mazei SLP. One domain displays a unique, highly symmetrical, seven-bladed beta propeller fold, and the other belongs to the polycystic kidney disease (PKD) superfamily fold. The third domain is predicted to adopt a beta helix fold. These domains have homologs in metazoan cell surface proteins, suggesting remarkable relationships between domains in archaeal SLPs and metazoan cell surface proteins.  相似文献   
945.
Acyl glucuronides of nonsteroidal anti-inflammatory drugs having a chiral center are known to be chemically very active and form covalently bound adducts with proteins, such as human serum albumin, which may be the cause of hypersensitive reactions. Hepatic acyl glucuronosyltransferase catalyzes the transformation of alpha-aryl propionates into these diastereoisomeric acyl glucuronides, and, hence, its activity needs to be characterized. From this point of view, we developed a rapid, accurate and reproducible analytical method for the separation and determination of diastereoisomeric glucuronides of flurbiprofen, one of the nonsteroidal anti-inflammatory drugs, in the incubation mixture of the hepatic microsomal preparation by high-performance liquid chromatography with a simple column-switching technique for deproteinization. The glucuronides were separated on a TSKgel ODS-80Ts column with 20 mM ammonium acetate buffer (pH 5.6)-ethanol-acetonitrile as the mobile phase and monitored with a UV detector at 246 nm. The detection limit of the proposed method was 600 fmol/injection at a signal-to-noise ratio of 10. The validation results indicated that this method would be very useful for the determination of diastereomeric acyl glucuronides formed from flurbiprofen in an incubation mixture.  相似文献   
946.
The frequency distributions of apolipoprotein C alleles in native Asian sheep (Bengal, Kagi, Lampuchhre, Vietnamese, Myanmar, Baruwal, Bhyanglung, Khalkhas, and Kuwait) were determined using a one-dimensional polyacrylamide gel isoelectric-focusing immunoblotting technique. Among these Asian sheep, the genetic locus consisted mainly of two common APOC*1 and APOC*3 alleles. The Baruwal sheep most frequently possessed APOC*1 (0.9881), showing significant differences from all other Asian sheep in allele frequency (0.7195-0.9032, P < 0.02). Compared with European sheep tested previously, these Asian sheep had significantly higher frequencies of APOC*1 (0.7828 and 0.7127 averages, P < 0.0005) and APOC*3 (0.2162 and 0.11 averages, P < 0.0001). In particular, APOC*2 was detected at an extremely low frequency (0.0025) in the Khalkhas sheep only, and was uncommon in all Asian sheep (0.001 average), in contrast with the 0.1773 average of European sheep (P < 0.00001). This finding suggests that APOC*2 is exceedingly rare in Asian sheep. With the exception of triglycerides and VLDL cholesterol in the Vietnamese sheep, no phenotypic effects on plasma lipid and lipoprotein levels in the Asian sheep tested were seen.  相似文献   
947.
Here, we show that fibronectin (FN) peptides derived from two distinct regions promote the insulin-induced adipocyte differentiation of ST-13 cells by preventing FN fibrillogenesis. ST-13 cells formed numerous FN fibrils under nonadipogenic conditions, whereas this FN fibrillogenesis was suppressed by adipose induction with insulin. The insulin-induced adipocyte differentiation was promoted by an amino-terminal 24-kDa fragment of FN, accompanied by further suppression of FN fibrillogenesis. The 24 K fragment prevented FN matrix assembly by direct incorporation into the FN matrix. Like the 24 K fragment, a peptide from the 14th type III repeat, termed FNIII14, which suppressed the integrin alpha 5 beta 1-mediated adhesion of ST-13 cells to FN, accelerated the adipocyte differentiation by preventing FN fibrillogenesis without direct incorporation into the FN matrix. FNIII14 induced the conformation change of beta1 integrins of K562 cells from active to resting, as judged by FACS analysis using a monoclonal antibody AG89 directed to an active beta1 integrin-dependent epitope. Binding of a (125)I-labeled FN fragment containing the RGD cell adhesive site to ST-13 cell surface was dissociated by FNIII14, with a concomitant binding of FNIII14 itself to the cell surface. The affinity labeling of ST-13 cells using biotinylated FNIII14 showed that FNIII14 specifically bound to a nonintegrin membrane protein with M(r) of around 50 kDa. Thus, the results indicated that prevention of FN fibrillogenesis by the 24 K Fib 1 fragment and FNIII14 caused the promotion of adipocyte differentiation of ST-13 cells and that the former was due to the direct incorporation into the FN matrix and that the latter might be interpreted by negative regulation of FN receptor alpha 5 beta 1 activity.  相似文献   
948.
In order to develop a protocol to treat brain metastatic melanoma using our 10B-p-boronophenylalanine (BPA) boron neutron capture therapy (BNCT), we initiated the following studies (i), Comparative analyses of boron biodistribution between melanoma proliferating in the brain and skin among melanotic and amelanotic types, and (ii) Therapeutic evaluation of BPA-BNCT for brain melanoma models of both types, using survival times. Our present data have revealed that boron concentration in melanoma proliferating in the brain, the major prerequisite for successful BNCT, showed a positive correlation to melanin synthesizing activity in the same way as melanoma proliferating in skin. Further, the boron concentration ratio of melanoma to normal surrounding tissue for brain melanoma models was considerably higher than that for subcutaneous (s.c.) ones because of the existence of the blood-brain barrier (BBB). Additionally, from analyses of median and mean survival times following BNCT using low, middle, and high neutron doses, the therapeutic effect of BNCT for the amelanotic A1059 melanoma appeared at first glance to be higher than that for the highly BPA attracting and highly relative biological effect equivalent dose obtaining B15b melanoma. As the survival time was dependent on both regression and regrowth curves, and because the brain melanoma model in small animals made it difficult to evaluate these curves separately, we further examined the in vivo growth curve of both types of melanomas following implantation in s.c. tissue. The melanotic B15b melanoma was indeed found to possess much higher growth rate as compared with that of the amelanotic A1059 melanoma. The significance of boron biodistribution studies and BNCT survival curve analyses in forming an effective clinical protocol for individual human cases of melanoma brain metastasis is discussed.  相似文献   
949.
The conformational transition states of a beta-hairpin peptide in explicit water were identified from the free energy landscapes obtained from the multicanonical ensemble, using an enhanced conformational sampling calculation. The beta-hairpin conformations were significant at 300 K in the landscape, and the typical nuclear Overhauser effect signals were reproduced, consistent with the previously reported experiment. In contrast, the disordered conformations were predominant at higher temperatures. Among the stable conformations at 300 K, there were several free energy barriers, which were not visible in the landscapes formed with the conventional parameters. We identified the transition states around the saddle points along the putative folding and unfolding paths between the beta-hairpin and the disordered conformations in the landscape. The characteristic features of these transition states are the predominant hydrophobic contacts and the several hydrogen bonds among the side-chains, as well as some of the backbone hydrogen bonds. The unfolding simulations at high temperatures, 400 K and 500 K, and their principal component analyses also provided estimates for the transition state conformations, which agreed well with those at 400 K and 500 K deduced from the current free energy landscapes at 400 K and 500 K, respectively. However, the transition states at high temperatures were much more widely distributed on the landscape than those at 300 K, and their conformations were different.  相似文献   
950.
Growth and development, and auxin polar transport in Arabidopsis thaliana transformed with iaaH gene were studied under simulated microgravity conditions on a three-dimensional (3-D) clinostat. Simulated microgravity conditions on a 3-D clinostat did not affect the number of rosette leaves but promoted the growth and development (fresh weight of plant and the elongation of flower stalk) of transformants. Final growth of transformants under simulated microgravity conditions on a 3-D clinostat was almost equivalent to that grown on 1 g conditions in the presence of 1 micromoles IAM (indole-3-acetamide). The activities of auxin polar transport in the segments of flower stalk (inflorescence axis) of transformants grown on 1 g conditions were significantly promoted by the addition of IAM. Interestingly, simulated microgravity conditions on a 3-D clinostat also promoted the activities of auxin polar transport of transformants grown on the medium with or without IAM. Based on the results in this study, transgenic plants may not have an efficient homeostatic mechanism for the control of growth and development, and auxin polar transport activity in microgravity conditions in space.  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