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   7338篇
  免费   683篇
  国内免费   6篇
  2023年   43篇
  2022年   80篇
  2021年   232篇
  2020年   153篇
  2019年   183篇
  2018年   180篇
  2017年   157篇
  2016年   210篇
  2015年   355篇
  2014年   380篇
  2013年   462篇
  2012年   549篇
  2011年   543篇
  2010年   321篇
  2009年   290篇
  2008年   380篇
  2007年   391篇
  2006年   330篇
  2005年   337篇
  2004年   315篇
  2003年   281篇
  2002年   272篇
  2001年   67篇
  2000年   43篇
  1999年   64篇
  1998年   83篇
  1997年   39篇
  1996年   33篇
  1995年   39篇
  1994年   30篇
  1993年   46篇
  1992年   46篇
  1991年   31篇
  1990年   31篇
  1989年   40篇
  1988年   29篇
  1987年   37篇
  1986年   34篇
  1985年   29篇
  1984年   36篇
  1983年   25篇
  1982年   43篇
  1981年   44篇
  1980年   42篇
  1979年   24篇
  1978年   39篇
  1977年   30篇
  1975年   33篇
  1974年   30篇
  1973年   29篇
排序方式: 共有8027条查询结果,搜索用时 31 毫秒
951.
952.
953.
A new near-infrared fluorescent compound containing two cyclic RGD motifs, cypate-[c(RGDfK)](2) (1), was synthesized based on a carbocyanine fluorophore bearing two carboxylic acid groups (cypate) for integrin α(v)β(3)-targeting. Compared with its monovalent counterpart cypate-c(RGDfK) (2), 1 exhibited remarkable improvements in integrin α(v)β(3) binding affinity and tumor uptake in nude mice of A549. The results suggest that cypate-linked divalent ligands can serve as an important molecular platform for exploring receptor-targeted optical imaging and treatment of various diseases.  相似文献   
954.
Discovery of a novel nor-seco himbacine analog as potent thrombin receptor (PAR-1) antagonist is described. Despite low plasma level, these new analogs showed excellent ex vivo efficacy in the monkey platelet aggregation assay. A potent hydroxy metabolite generated in vivo was identified as the agent responsible for the ex vivo efficacy. Following this discovery, the metabolite series was optimized to obtain analogs that showed very good ex vivo efficacy along with excellent pharmacokinetic profile in c. monkey.  相似文献   
955.
A series of α7 nicotinic acetylcholine receptor full-agonists with a 1,3,4-oxadiazol-2-amine core has been discovered. Systematic exploration of the structure-activity relationships for both α7 potency and selectivity with respect to interaction with the hERG channel are described. Further profiling led to the identification of compound 22, a potent full agonist showing efficacy in the novel object recognition model of cognition enhancement.  相似文献   
956.
957.
A Tnt1-insertion mutant population of Medicago truncatula ecotype R108 was screened for defects in nodulation and symbiotic nitrogen fixation. Primary screening of 9,300 mutant lines yielded 317 lines with putative defects in nodule development and/or nitrogen fixation. Of these, 230 lines were rescreened, and 156 lines were confirmed with defective symbiotic nitrogen fixation. Mutants were sorted into six distinct phenotypic categories: 72 nonnodulating mutants (Nod-), 51 mutants with totally ineffective nodules (Nod+ Fix-), 17 mutants with partially ineffective nodules (Nod+ Fix+/-), 27 mutants defective in nodule emergence, elongation, and nitrogen fixation (Nod+/- Fix-), one mutant with delayed and reduced nodulation but effective in nitrogen fixation (dNod+/- Fix+), and 11 supernodulating mutants (Nod++Fix+/-). A total of 2,801 flanking sequence tags were generated from the 156 symbiotic mutant lines. Analysis of flanking sequence tags revealed 14 insertion alleles of the following known symbiotic genes: NODULE INCEPTION (NIN), DOESN'T MAKE INFECTIONS3 (DMI3/CCaMK), ERF REQUIRED FOR NODULATION, and SUPERNUMERARY NODULES (SUNN). In parallel, a polymerase chain reaction-based strategy was used to identify Tnt1 insertions in known symbiotic genes, which revealed 25 additional insertion alleles in the following genes: DMI1, DMI2, DMI3, NIN, NODULATION SIGNALING PATHWAY1 (NSP1), NSP2, SUNN, and SICKLE. Thirty-nine Nod- lines were also screened for arbuscular mycorrhizal symbiosis phenotypes, and 30 mutants exhibited defects in arbuscular mycorrhizal symbiosis. Morphological and developmental features of several new symbiotic mutants are reported. The collection of mutants described here is a source of novel alleles of known symbiotic genes and a resource for cloning novel symbiotic genes via Tnt1 tagging.  相似文献   
958.
Oreopithecus bambolii is a Late Miocene hominoid with an extensive fossil record in the Baccinello Basin (Tuscany, Italy), and was the only western European hominoid to survive a major extinction event ca. 9.6 Ma (millions of years ago). Oreopithecus lived in the insular Tusco-Sardinian paleobioprovince, where it evolved many unique anatomical specializations that make it important for understanding the mechanisms and history of Late Miocene hominoid evolution. The eventual extinction of Oreopithecus and its associated fauna ca. 6.5 Ma has generally been attributed to interaction with species that arrived from continental Europe following tectonic collision of the Tusco-Sardinian province with mainland Italy, but palynological, paleontological, and sedimentological records indicate an environmental shift toward more variable climate across the extinction event.To explore the possibility of environmental change as a contributing factor in the extinction of Oreopithecus, we developed a stable carbon and oxygen isotope record from organic matter in paleosols from the Baccinello Basin. These data show very low temporal and spatial variability (indicating plant ecosystem stability through time and space) and provide no evidence for ecologically significant changes in floral composition spanning the extinction event, suggesting that environmental change was not an underlying cause for the extinction of Oreopithecus and its associated fauna. The carbon isotope values fall entirely within the range of isotopic variability for modern plants following the C3 photosynthetic pathway (trees, shrubs, cool-season grasses), indicating that C4 vegetation (warm-season grasses) was not an important component of biomass. When corrected for temporal variation in the carbon isotopic composition of atmospheric carbon dioxide, the paleosol carbon isotope values are consistent with predicted values based on modern plants and the Baccinello palynoflora, supporting the reliability of paleosol isotopic records as paleoecological proxies.  相似文献   
959.
Rational modification of the clinically tested CGRP receptor antagonist MK-3207 (3) afforded an analogue with increased unbound fraction in rat plasma and enhanced aqueous solubility, 2-[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(6S)-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl]acetamide (MK-8825) (6). Compound 6 maintained similar affinity to 3 at the human and rat CGRP receptors but possessed significantly improved in vivo potency in a rat pharmacodynamic model. The overall profile of 6 indicates it should find utility as a rat tool to investigate effects of CGRP receptor blockade in vivo.  相似文献   
960.
Collins CM  Speck SH 《PloS one》2012,7(3):e33230
Infection of mice with murine gammaherpesvirus 68 (MHV68) provides a tractable small animal model to study various aspects of persistent gammaherpesvirus infection. We have previously utilized a transgenic MHV68 that expresses enhanced yellow fluorescent protein (EYFP) to identify infected cells. While this recombinant MHV68 has been useful for identifying infected cell populations by flow cytometry, it has been suboptimal for identification of infected cells in tissue sections due to the high solubility of EYFP. Efficient detection of EYFP expressed from the MHV68 genome in tissue sections requires fixation of whole organs prior to sectioning, which frequently leads to over-fixation of some cellular antigens precluding their detection. To circumvent this issue, we describe the generation and characterization of a transgenic MHV68 harboring a fusion gene composed of the EYFP coding sequence fused to the histone H2B open reading frame. Because the H2bYFP fusion protein is tightly bound in nucleosomes in the nucleus it does not freely diffuse out of unfixed tissue sections, and thus eliminates the need for tissue fixation. We have used the MHV68-H2bYFP recombinant virus to assess the location and distribution of virus infected B cells in germinal centers during the peak of MHV68 latency in vivo. These analyses show that the physical location of distinct populations of infected germinal center B cells correlates well with their surface phenotype. Furthermore, analysis of the distribution of virus infection within germinal center B cell populations revealed that ca. 70% of MHV68 infected GC B cells are rapidly dividing centroblasts, while ca. 20% have a clear centrocyte phenotype. Finally, we have shown that marking of infected cells with MHV68-H2bYFP is extended long after the onset of latency - which should facilitate studies to track MHV68 latently infected cells at late times post-infection.  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