全文获取类型
收费全文 | 2648篇 |
免费 | 207篇 |
国内免费 | 1篇 |
专业分类
2856篇 |
出版年
2023年 | 9篇 |
2022年 | 22篇 |
2021年 | 41篇 |
2020年 | 16篇 |
2019年 | 24篇 |
2018年 | 26篇 |
2017年 | 34篇 |
2016年 | 61篇 |
2015年 | 107篇 |
2014年 | 111篇 |
2013年 | 144篇 |
2012年 | 226篇 |
2011年 | 176篇 |
2010年 | 117篇 |
2009年 | 119篇 |
2008年 | 223篇 |
2007年 | 155篇 |
2006年 | 165篇 |
2005年 | 148篇 |
2004年 | 150篇 |
2003年 | 134篇 |
2002年 | 137篇 |
2001年 | 22篇 |
2000年 | 16篇 |
1999年 | 31篇 |
1998年 | 45篇 |
1997年 | 24篇 |
1996年 | 18篇 |
1995年 | 30篇 |
1994年 | 23篇 |
1993年 | 17篇 |
1992年 | 20篇 |
1991年 | 16篇 |
1990年 | 12篇 |
1989年 | 12篇 |
1988年 | 16篇 |
1987年 | 13篇 |
1986年 | 13篇 |
1985年 | 18篇 |
1984年 | 12篇 |
1983年 | 13篇 |
1982年 | 15篇 |
1981年 | 21篇 |
1980年 | 17篇 |
1978年 | 15篇 |
1977年 | 12篇 |
1976年 | 7篇 |
1974年 | 10篇 |
1973年 | 10篇 |
1968年 | 6篇 |
排序方式: 共有2856条查询结果,搜索用时 0 毫秒
101.
Verotoxin 1 binding to intestinal crypt epithelial cells results in localization to lysosomes and abrogation of toxicity 总被引:2,自引:0,他引:2
Verotoxins (VTs) are important virulence factors of enterohaemorrhagic Escherichia coli (EHEC), a group of bacteria associated with severe disease sequelae in humans. The potent cytotoxic activity of VTs is important in pathogenicity, resulting in the death of cells expressing receptor Gb3 (globotriaosylceramide). EHEC, particularly serotype O157:H7, frequently colonize reservoir hosts (such as cattle) in the absence of disease, however, the basis to avirulence in this host has been unclear. The objective of this study was assessment of interaction between VT and intestinal epithelium, which represents the major interface between the host and enteric organisms. Bovine intestinal epithelial cells expressed Gb3 in vitro in primary cell cultures, localizing specifically to proliferating crypt cells in corroboration with in situ immunohistological observations on intestinal mucosa. Expression of receptor by these cells contrasts with the absence of Gb3 on human intestinal epithelium in vivo. Despite receptor expression, VT exhibited no cytotoxic activity against bovine epithelial cells. Sub-cellular localization of VT indicated that this toxin was excluded from endoplasmic reticulum but localized to lysosomes, corresponding with abrogation of cytotoxicity. VT intracellular trafficking was unaffected by treatment of primary cell cultures with methyl-beta-cyclodextrin, indicating that Gb3 in these cells is not associated with lipid rafts but is randomly distributed in the membrane. The combination of Gb3 isoform, membrane distribution and VT trafficking correlate with observations of other receptor-positive cells that resist verocytotoxicity. These studies demonstrate that intestinal epithelium is an important determinant in VT interaction with major implications for the differential consequences of EHEC infection in reservoir hosts and humans. 相似文献
102.
103.
Tam SL Sims E Kaufman S 《American journal of physiology. Regulatory, integrative and comparative physiology》2002,283(4):R827-R831
Atrial distension increases c-fos expression in the paraventricular nucleus of virgin, but not pregnant, rats. We proposed that nitric oxide (NO), biosynthesis of which increases during pregnancy, blunts this reflex and that blocking NO biosynthesis would restore the response. Female rats were implanted with indwelling intracardiac balloons. On day 14 of pregnancy, osmotic minipumps containing either D- or N(G)-nitro-L-arginine methyl ester (L-NAME) (120 mg/2 ml at 10 microg/min) were implanted. On day 20, the rats were infused with saline (3 ml/h) with or without atrial balloon inflation (1 h). The brains were then processed for quantitation of c-fos expression. In the virgin rats, and in the pregnant rats treated with L-NAME, atrial distension significantly increased hypothalamic c-fos expression. In the pregnant animals treated with D-NAME, the response was greatly attenuated. NO had no effect on the increase in atrial receptor afferent discharge (single-fiber recordings) elicited by atrial distension. We conclude that, during pregnancy, NO attenuates central processing of the reflex response to atrial distension but does not alter the transducer properties of the volume receptors. 相似文献
104.
Summary For numerical solution of the reaction-mass transfer equations for immobilised biocatalysts it may be better to start integration at the particle surface and proceed inwards: calculations are targetted on the region to which practically interesting changes are often confined (because concentrations are effectively zero in the interior); and during iterative solution wrong initial estimates may be rejected after detecting anomalies early in the integration.Symbols Cb
substrate concentration in bulk (mol m–3)
- c
dimensionless substrate concentration (C/Cb) (-)
- De
effective diffusion coefficient (m2s–1)
- Da
Damkohler number (V.ro
2/De.Ks) (-)
- Ks
substrate concentration kinetic coefficient (mol m–3)
- ke
external mass transfer coefficient (ms–1)
- ro
bead radius (m)
- Sh
Sherwood number (ke.ro/De) (-)
- V
maximum rate per unit volume in beads (mol m–3s–1)
- x
dimensionless distance from bead centre (r/ro) (-)
-
dimensionless kinetic coefficient (Ks/Cb) (-)
- o
effectiveness factor (-) 相似文献
105.
Elaine K. Perry Elizabeth Marshall Janet Kerwin Carthage J. Smith † Sabiha Jabeen Anthony V. Cheng Robert H. Perry† 《Journal of neurochemistry》1990,55(4):1454-1456
Senile dementia of Lewy body type is characterized clinically by a relatively acute onset of fluctuating memory loss and confusion, frequently accompanied by visual hallucinations. Neurochemical analyses of temporal cortex has revealed a distinction between hallucinating and nonhallucinating patients in both cholinergic and monaminergic transmitter activities. In contrast with the cholinergic enzyme choline acetyltransferase, which was more extensively reduced in hallucinating individuals, serotonergic S2 receptor binding and both dopamine and serotonin metabolites were significantly decreased in nonhallucinating cases. These results suggest that an imbalance between monaminergic and cholinergic transmitters is involved in hallucinogenesis in the human brain. 相似文献
106.
Joe B Remmers EF Dobbins DE Salstrom JL Furuya T Dracheva S Gulko PS Cannon GW Griffiths MM Wilder RL 《Immunogenetics》2000,51(11):930-944
Rat Chromosome 10 (RNO10) harbors Cia5, a non-MHC quantitative trait locus (QTL) that regulates the severity of type II collagen-induced arthritis (CIA) in DAxF344 and DAxBN F2 rats. CIA is an animal model with many features that resemble rheumatoid arthritis. To facilitate analysis of Cia5 independently of the other CIA regulatory loci on other chromosomes, DA recombinant QTL speed congenic rats, DA.F344(Cia5), were generated. These QTL congenic rats have a large chromosomal segment containing Cia5 (interval size < or =80.1 cM) from CIA-resistant F344 rats introgressed into their genome. Phenotypic analyses of these rats for susceptibility and severity of CIA confirmed that Cia5 is an important disease-modifying locus. CIA severity was significantly lower in the Cia5 congenic rats than in DA controls. We also generated DA Cia5 speed sub-congenic rats, DA.F344(Cia5a), which had a smaller segment of the F344 genome, Cia5a, comprising only the distal q-telomeric end (interval size < or = 22.5 cM) of Cia5, introgressed into their genome. DA.F344(Cia5a) sub-congenic rats also exhibited reduced CIA disease severity compared with the parental DA rats. The regulatory effects in both congenic strains were sex influenced. The disease-ameliorating effect of the larger fragment, Cia5, was greater in males than in females, but the effect of the smaller fragment, Cia5a, was greater in females. We also present an improved genetic linkage map covering the Cia5/Cia5a region, which we have integrated with two rat radiation hybrid maps. Comparative homology analysis of this genomic region with mouse and human chromosomes was also undertaken. Regulatory loci for multiple autoimmune/inflammatory diseases in rats (RNO10), mice (MMU11), and humans (HSA17 and HSA5q23-q31) map to chromosomal segments homologous to Cia5 and Cia5a. 相似文献
107.
Richard E. McNicol Eberhard Scherer Elaine J. Murkin 《Environmental Biology of Fishes》1985,12(3):219-229
Synopsis Direct observations of young-of-the-year brook charr, Salvelinus fontinalis, in a second-order woodland stream indicated that most of their feeding effort was directed toward sub-surface, drifting prey (83% of feeding time). Feeding from the substrate and water surface was much less frequent (17% of feeding time). Comparisons of gut contents to drift net and substrate fauna samples corroborated that the most commonly consumed prey (chironomid and trichopteran larvae, ostracods, and ephemeropteran nymphs) were captured primarily from sub-surface, invertebrate drift. The disproportionate numbers of some prey species in the guts of several fish indicate that some prey selection occurred. Territories appeared to be cardioid-shaped, and were often contiguous, with dominance hierarchies evident among the residents. Agonistic interactions were frequent. Charges and chases predominated (91% of interactions) while lateral displays were infrequent (9% of interactions). Overall, these fish spent most of the daylight hours station-holding (77%) and feeding (18%). While only 3% of total time was spent in aggression, this amounted to 14% of the time a fish spent away from its station. There was some indication that territories were defended at a cost of feeding time. 相似文献
108.
Within-cluster resampling 总被引:1,自引:0,他引:1
109.
Mark E. Lauer Tibor T. Glant Katalin Mikecz Paul L. DeAngelis F. Michael Haller M. Elaine Husni Vincent C. Hascall Anthony Calabro 《The Journal of biological chemistry》2013,288(1):205-214
The covalent transfer of heavy chains (HCs) from inter-α-inhibitor (IαI) to hyaluronan (HA) via the protein product of tumor necrosis factor-stimulated gene-6 (TSG-6) forms the HC-HA complex, a pathological form of HA that promotes the adhesion of leukocytes to HA matrices. The transfer of HCs to high molecular weight (HMW) HA is a reversible event whereby TSG-6 can shuffle HCs from one HA molecule to another. Therefore, HMW HA can serve as both an HC acceptor and an HC donor. In the present study, we show that transfer of HCs to low molecular weight HA oligosaccharides is an irreversible event where subsequent shuffling does not occur, i.e. HA oligosaccharides from 8 to 21 monosaccharide units in length can serve as HC acceptors, but are unable to function as HC donors. We show that the HC-HA complex is present in the synovial fluid of mice subjected to systemic and monoarticular mouse models of rheumatoid arthritis. Furthermore, we demonstrate that HA oligosaccharides can be used, with TSG-6, to irreversibly shuffle HCs from pathological, HMW HC-HA to HA oligosaccharides, thereby restoring HC-HA matrices from the inflamed joint to their normal state, unmodified with HCs. This process was also effective for HC-HA in the synovial fluid of human rheumatoid arthritis patients (in vitro). 相似文献
110.
Anna Nolan Elaine Fajardo Maryann L. Huie Rany Condos Anil Pooran Rodney Dawson Keertan Dheda Eric Bateman William N. Rom Michael D. Weiden 《PloS one》2013,8(3)