全文获取类型
收费全文 | 2821篇 |
免费 | 234篇 |
国内免费 | 4篇 |
出版年
2023年 | 20篇 |
2022年 | 40篇 |
2021年 | 103篇 |
2020年 | 49篇 |
2019年 | 65篇 |
2018年 | 77篇 |
2017年 | 54篇 |
2016年 | 90篇 |
2015年 | 171篇 |
2014年 | 195篇 |
2013年 | 217篇 |
2012年 | 218篇 |
2011年 | 229篇 |
2010年 | 150篇 |
2009年 | 116篇 |
2008年 | 165篇 |
2007年 | 163篇 |
2006年 | 142篇 |
2005年 | 138篇 |
2004年 | 134篇 |
2003年 | 114篇 |
2002年 | 82篇 |
2001年 | 19篇 |
2000年 | 12篇 |
1999年 | 17篇 |
1998年 | 26篇 |
1997年 | 18篇 |
1996年 | 9篇 |
1995年 | 18篇 |
1994年 | 21篇 |
1993年 | 22篇 |
1992年 | 12篇 |
1991年 | 12篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 10篇 |
1985年 | 12篇 |
1984年 | 8篇 |
1983年 | 8篇 |
1982年 | 11篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 5篇 |
1976年 | 7篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1971年 | 4篇 |
排序方式: 共有3059条查询结果,搜索用时 62 毫秒
991.
Bungard CJ Hartman GD Manikowski JJ Perkins JJ Bai C Brandish PE Euler DH Hershey JC Schmidt A Fang Y Norcross RT Rushmore TH Thompson CD Meissner RS 《Bioorganic & medicinal chemistry》2011,19(24):7374-7386
A series of partial agonists of the Glucocorticoid Receptor were prepared targeting reduced transactivation activity, while maintaining significant transrepression activity. Incorporation of an ortho-aryl amide produced compounds with the desired in vitro profile. Bioreactors consisting of Suspension cultures of Sf21 cells co expressing a CYP3A4 and NADPH-cytochrome P450 oxireductase were used to prepare the major metabolites of these compounds and revealed that oxidative N-dealkylation provided a pathway for formation of metabolites that were more agonistic than the parent partial agonists. Oxidative N-dealkylation was blocked in a new series of compounds, however oxidation alone was capable of producing full agonist metabolites. Incorporation of an ortho-primary amide and utilization of fluorine to modulate agonism afforded partial agonist MK-5932. Synthesis of the major metabolites of MK-5932 using bioreactor technology revealed that no significant GR-active metabolites were formed. Orally administered MK-5932 displayed anti-inflammatory efficacy in a Rat Oxazolone-induced chronic dermatitis model, while sparing plasma insulin. 相似文献
992.
We recorded 31 species in the stomachs of 146 coastal bottlenose dolphins ( Tursiops truncatus ) from North Carolina, U. S. A. Sciaenid fishes were the most common prey (frequency of occurrence = 95%). By mass, Atlantic croaker ( Micropogonias undulatus ) dominated the diet of dolphins that stranded inside estuaries, whereas weakfish ( Cynosicon regalis ) was most important for dolphins in the ocean. Inshore squid ( Loligo sp.) was eaten commonly by dolphins in the ocean, but not by those in the estuaries. There was no significant pattern in prey size associated with dolphin demography, but the proportion of the diet represented by croaker was higher for males than for females, and mature dolphins ate more croaker than did juveniles. Dietary differences between dolphins that stranded in the estuaries and those that stranded on ocean beaches support the hypothesis that some members of the population inhabit the ocean primarily while others reside principally in estuaries. The overwhelming majority of prey were soniferous species (75% of numerical abundance), which is consistent with the hypothesis that bottlenose dolphins use passive listening to locate noise-making fishes. However, spatiotemporal patterns in consumption of Sciaenid fishes did not coincide with their spawning, which is when peak sound production is thought to occur. 相似文献
993.
Skropeta D Settasatian C McMahon MR Shearston K Caiazza D McGrath KC Jin W Rader DJ Barter PJ Rye KA 《Journal of lipid research》2007,48(9):2047-2057
Endothelial lipase (EL) is a member of the triglyceride lipase gene family with high phospholipase and low triacylglycerol lipase activities and a distinct preference for hydrolyzing phospholipids in HDL. EL has five potential N-glycosylation sites, four of which are glycosylated. The aim of this study was to determine how glycosylation affects the phospholipase activity of EL in physiologically relevant substrates. Site-directed mutants of EL were generated by replacing asparagine (N) 62, 118, 375, and 473 with alanine (A). These glycan-deficient mutants were used to investigate the kinetics of phospholipid hydrolysis in fully characterized preparations of spherical reconstituted high density lipoprotein (rHDL) containing apolipoprotein E2 (apoE2) [(E2)rHDL], apoE3 [(E3)rHDL], apoE4 [(E4)rHDL], or apoA-I [(A-I)rHDL] as the sole apolipoprotein. Wild-type EL hydrolyzed the phospholipids in (A-I)rHDL, (E2)rHDL, (E3)rHDL, and (E4)rHDL to similar extents. The phospholipase activities of EL N118A, EL N375A, and EL N473A were significantly diminished relative to that of wild-type EL, with the greatest reduction being apparent for (E3)rHDL. The phospholipase activity of EL N62A was increased up to 6-fold relative to that of wild-type EL, with the greatest enhancement of activity being observed for (E2)rHDL. These data show that individual N-linked glycans have unique and important effects on the phospholipase activity and substrate specificity of EL. 相似文献
994.
Hewat EA Durmort C Jacquamet L Concord E Gulino-Debrac D 《Journal of molecular biology》2007,365(3):744-751
Vascular endothelial-cadherin (VE-cadherin) is the major constituent of the adherens junctions of endothelial cells and plays a key role in angiogenesis and vascular permeability. The ectodomains EC1-4 of VE-cadherin are known to form hexamers in solution. To examine the mechanism of homotypic association of VE-cadherin, we have made a 3D reconstruction of the EC1-4 hexamer using electron microscopy and produced a homology model based on the known structure of C-cadherin EC1-5. The hexamer consists of a trimer of dimers with each N-terminal EC1 module making an antiparallel dimeric contact, and the EC4 modules forming extensive trimeric interactions. Each EC1-4 molecule makes a helical curve allowing some torsional flexibility to the edifice. While there is no direct evidence for the existence of hexamers of cadherin at adherens junctions, the model that we have produced provides indirect evidence since it can be used to explain some of the disparate results for adherens junctions. It is in accord with the X-ray and electron microscopy results, which demonstrate that the EC1 dimer is central to homotypic cadherin interaction. It provides an explanation for the force measurements of the interaction between opposing cadherin layers, which have previously been interpreted as resulting from three different interdigitating interactions. It is in accord with observations of native junctions by cryo-electron microscopy. The fact that this hexameric model of VE-cadherin can be used to explain more of the existing data on adherens junctions than any other model alone argues in favour of the existence of the hexamer at the adherens junction. In the context of the cell-cell junction these cis-trimers close to the membrane, and trans-dimers from opposing membranes, would increase the avidity of the bond. 相似文献
995.
996.
The present study shows that the relative contributions of leaf area ratio (LAR) and net assimilation rate (NAR) to variation among species in relative growth rate (RGR) depend on growth temperature. We grew three subantarctic and three alpine Poa species at daytime temperatures of 7, 12 and 17 degrees C, and analysed interspecific and temperature-related variation in RGRs by growth analysis. Variation in NAR accounted for most of the interspecific differences in RGR at low growth temperature, whereas variation in both NAR and LAR contributed strongly to interspecific differences in RGR at high growth temperature. For most species, the increase in RGR from 7 to 12 degrees C was attributable to an increase in LAR, whereas the increase in RGR from 12 to 17 degrees C was attributable to an increase in NAR. There were no differences between native subantarctic and alpine species in the plasticity of growth responses to temperature. However, Poa annua, a species introduced to the subantarctic, showed much greater growth plasticity than other species. There was little difference among species in tolerance of high-temperature extremes. 相似文献
997.
998.
In filamentous fungi, RNA silencing is an attractive alternative to disruption experiments for the functional analysis of genes. We adapted the gene encoding the autofluorescent DsRed protein as a reporter to monitor the silencing process in fungal transformants. Using the cephalosporin C producer Acremonium chrysogenum, strains showing a high level of expression of the DsRed gene were constructed, resulting in red fungal colonies. Transfer of a hairpin-expressing vector carrying fragments of the DsRed gene allowed efficient silencing of DsRed expression. Monitoring of this process by Northern hybridization, real-time PCR quantification, and spectrofluorometric measurement of the DsRed protein confirmed that downregulation of gene expression can be observed at different expression levels. The usefulness of the DsRed silencing system was demonstrated by investigating cosilencing of DsRed together with pcbC, encoding the isopenicillin N synthase, an enzyme involved in cephalosporin C biosynthesis. Downregulation of pcbC can be detected easily by a bioassay measuring the antibiotic activity of individual strains. In addition, the presence of the isopenicillin N synthase was investigated by Western blot hybridization. All transformants having a colorless phenotype showed simultaneous downregulation of the pcbC gene, albeit at different levels. The RNA-silencing system presented here should be a powerful genetic tool for strain improvement and genome-wide analysis of this biotechnologically important filamentous fungus. 相似文献
999.
Vibrio cholerae strains possess multiple strategies for abiotic and biotic surface colonization 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Mueller RS McDougald D Cusumano D Sodhi N Kjelleberg S Azam F Bartlett DH 《Journal of bacteriology》2007,189(14):5348-5360
Despite its notoriety as a human pathogen, Vibrio cholerae is an aquatic microbe suited to live in freshwater, estuarine, and marine environments where biofilm formation may provide a selective advantage. Here we report characterization of biofilms formed on abiotic and biotic surfaces by two non-O1/O139 V. cholerae strains, TP and SIO, and by the O1 V. cholerae strain N16961 in addition to the isolation of 44 transposon mutants of SIO and TP impaired in biofilm formation. During the course of characterizing the mutants, 30 loci which have not previously been associated with V. cholerae biofilms were identified. These loci code for proteins which perform a wide variety of functions, including amino acid metabolism, ion transport, and gene regulation. Also, when the plankton colonization abilities of strains N16961, SIO, and TP were examined, each strain showed increased colonization of dead plankton compared with colonization of live plankton (the dinoflagellate Lingulodinium polyedrum and the copepod Tigriopus californicus). Surprisingly, most of the biofilm mutants were not impaired in plankton colonization. Only mutants impaired in motility or chemotaxis showed reduced colonization. These results indicate the presence of both conserved and variable genes which influence the surface colonization properties of different V. cholerae subspecies. 相似文献
1000.
Nightingale RW Carol Chancey V Ottaviano D Luck JF Tran L Prange M Myers BS 《Journal of biomechanics》2007,40(3):535-542
New vehicle safety standards are designed to limit the amount of neck tension and extension seen by out-of-position motor vehicle occupants during airbag deployments. The criteria used to assess airbag injury risk are currently based on volunteer data and animal studies due to a lack of bending tolerance data for the adult cervical spine. This study provides quantitative data on the flexion-extension bending properties and strength on the male cervical spine, and tests the hypothesis that the male is stronger than the female in pure bending. An additional objective is to determine if there are significant differences in stiffness and strength between the male upper and lower cervical spine. Pure-moment flexibility and failure testing was conducted on 41 male spinal segments (O-C2, C4-C5, C6-C7) in a pure-moment test frame and the results were compared with a previous study of females. Failures were conducted at approximately 90 N-m/s. In extension, the male upper cervical spine (O-C2) fails at a moment of 49.5 (s.d. 17.6)N-m and at an angle of 42.4 degrees (s.d. 8.0 degrees). In flexion, the mean moment at failure is 39.0 (s.d. 6.3 degrees) N-m and an angle of 58.7 degrees (s.d. 5.1 degrees). The difference in strength between flexion and extension is not statistically significant. The difference in the angles is statistically significant. The upper cervical spine was significantly stronger than the lower cervical spine in both flexion and extension. The male upper cervical spine was significantly stiffer than the female and significantly stronger than the female in flexion. Odontoid fractures were the most common injury produced in extension, suggesting a tensile mechanism due to tensile loads in the odontoid ligamentous complex. 相似文献