全文获取类型
收费全文 | 883篇 |
免费 | 69篇 |
国内免费 | 2篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 9篇 |
2020年 | 9篇 |
2019年 | 4篇 |
2018年 | 12篇 |
2017年 | 10篇 |
2016年 | 18篇 |
2015年 | 23篇 |
2014年 | 34篇 |
2013年 | 40篇 |
2012年 | 40篇 |
2011年 | 43篇 |
2010年 | 42篇 |
2009年 | 35篇 |
2008年 | 55篇 |
2007年 | 63篇 |
2006年 | 50篇 |
2005年 | 60篇 |
2004年 | 61篇 |
2003年 | 58篇 |
2002年 | 30篇 |
2001年 | 9篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 15篇 |
1997年 | 10篇 |
1996年 | 9篇 |
1995年 | 9篇 |
1994年 | 14篇 |
1993年 | 16篇 |
1992年 | 14篇 |
1991年 | 12篇 |
1990年 | 10篇 |
1989年 | 10篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 7篇 |
1985年 | 12篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1978年 | 10篇 |
1977年 | 8篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 6篇 |
排序方式: 共有954条查询结果,搜索用时 15 毫秒
71.
72.
73.
Frisby CL Fraser RJ Schirmer MB Yeoh EK Blackshaw LA 《American journal of physiology. Gastrointestinal and liver physiology》2007,293(1):G121-G127
Administration of abdominal radiotherapy results in small intestinal motor dysfunction. We have developed a rat radiation enteritis model that, after exposure in vivo, shows high-amplitude, long-duration (HALD) pressure waves in ex vivo ileal segments. These resemble in vivo dysmotility where giant contractions migrate both antegradely and retrogradely. Mediation of these motor patterns is unclear, although enteric neural components are implicated. After the induction of acute radiation enteritis in vivo, ileal segments were isolated and arterially perfused. TTX, hexamethonium, atropine, or the selective muscarinic antagonists pirenzepine (M(1)), methoctramine (M(2)), and 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; M(3)) were added to the perfusate. The baseline mean rate per minute per channel of HALD pressure waves was 0.35 +/- 0.047. This was significantly reduced by TTX (83.3%, P < 0.01), hexamethonium (90.3%, P < 0.03), and atropine (98.4%, P < 0.01). The HALD pressure wave mean rate per minute per channel was significantly reduced by pirenzepine (81.1%, P < 0.03), methoctramine (96.8%, P < 0.001), and 4-DAMP (93.1%, P < 0.03) compared with predrug baseline data. As an indicator of normal motility patterns, the frequency of low-amplitude, short-duration pressure waves was also assessed. The mean rate per minute per channel of 5.15 +/- 0.98 was significantly increased by TTX (19%, P < 0.05) but significantly reduced by pirenzepine (35.1%, P < 0.02) and methoctramine (75%, P < 0.0003). However, the rate of small-amplitude pressure waves was not affected by hexamethonium, atropine, or the M(3) antagonist 4-DAMP. The data indicate a role for neuronal mechanisms and the specific involvement of cholinergic receptors in generating dysmotility in acute radiation enteritis. The effect of selective M(3) receptor antagonism suggests that M(3) receptors may provide specific therapeutic targets in acute radiation enteritis. 相似文献
74.
In vivo depletion of CD11c+ cells impairs scrapie agent neuroinvasion from the intestine 总被引:2,自引:0,他引:2
Raymond CR Aucouturier P Mabbott NA 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(11):7758-7766
Following oral exposure, some transmissible spongiform encephalopathy (TSE) agents accumulate first upon follicular dendritic cells (DCs) in the GALT. Studies in mice have shown that TSE agent accumulation in the GALT, in particular the Peyer's patches, is obligatory for the efficient transmission of disease to the brain. However, the mechanism through which TSE agents are initially conveyed from the gut lumen to the GALT is not known. Studies have implicated migratory hemopoietic DCs in this process, but direct demonstration of their involvement in vivo is lacking. In this study, we have investigated the contribution of CD11c(+) DCs in scrapie agent neuroinvasion through use of CD11c-diptheria toxin receptor-transgenic mice in which CD11c(+) DCs can be specifically and transiently depleted. Using two distinct scrapie agent strains (ME7 and 139A scrapie agents), we show that when CD11c(+) DCs were transiently depleted in the GALT and spleen before oral exposure, early agent accumulation in these tissues was blocked. In addition, CD11c(+) cell depletion reduced susceptibility to oral scrapie challenge indicating that TSE agent neuroinvasion from the GALT was impaired. In conclusion, these data demonstrate that migratory CD11c(+) DCs play a key role in the translocation of the scrapie agent from the gut lumen to the GALT from which neuroinvasion subsequently occurs. 相似文献
75.
Müller P Ewers C Bertsche U Anstett M Kallis T Breukink E Fraipont C Terrak M Nguyen-Distèche M Vollmer W 《The Journal of biological chemistry》2007,282(50):36394-36402
Bacterial cell division requires the coordinated action of cell division proteins and murein (peptidoglycan) synthases. Interactions involving the essential cell division protein FtsN and murein synthases were studied by affinity chromatography with membrane fraction. The murein synthases PBP1A, PBP1B, and PBP3 had an affinity to immobilized FtsN. FtsN and PBP3, but not PBP1A, showed an affinity to immobilized PBP1B. The direct interaction between FtsN and PBP1B was confirmed by pulldown experiments and surface plasmon resonance. The interaction was also detected by bacterial two-hybrid analysis. FtsN and PBP1B could be cross-linked in intact cells of the wild type and in cells depleted of PBP3 or FtsW. FtsN stimulated the in vitro murein synthesis activities of PBP1B. Thus, FtsN could have a role in controlling or modulating the activity of PBP1B during cell division in Escherichia coli. 相似文献
76.
77.
Mainardi JL Hugonnet JE Rusconi F Fourgeaud M Dubost L Moumi AN Delfosse V Mayer C Gutmann L Rice LB Arthur M 《The Journal of biological chemistry》2007,282(42):30414-30422
The beta-lactam antibiotics mimic the D-alanyl(4)-D-alanine(5) extremity of peptidoglycan precursors and act as "suicide" substrates of the DD-transpeptidases that catalyze the last cross-linking step of peptidoglycan synthesis. We have previously shown that bypass of the dd-transpeptidases by the LD-transpeptidase of Enterococcus faecium (Ldt(fm)) leads to high level resistance to ampicillin. Ldt(fm) is specific for the L-lysyl(3)-D-alanine(4) bond of peptidoglycan precursors containing a tetrapeptide stem lacking D-alanine(5). This specificity was proposed to account for resistance, because the substrate of Ldt(fm) does not mimic beta-lactams in contrast to the D-alanyl(4)-D-alanine(5) extremity of pentapeptide stems used by the DD-transpeptidases. Here, we unexpectedly show that imipenem, a beta-lactam of the carbapenem class, totally inhibited Ldt(fm) at a low drug concentration that was sufficient to inhibit growth of the bacteria. Peptidoglycan cross-linking was also inhibited, indicating that Ldt(fm) is the in vivo target of imipenem. Stoichiometric and covalent modification of Ldt(fm) by imipenem was detected by mass spectrometry. The modification was mapped into the trypsin fragment of Ldt(fm) containing the catalytic Cys residue, and the Cys to Ala substitution prevented imipenem binding. The mass increment matched the mass of imipenem, indicating that inactivation of Ldt(fm) is likely to involve rupture of the beta-lactam ring and acylation of the catalytic Cys residue. Thus, the spectrum of activity of beta-lactams is not restricted to transpeptidases of the DD-specificity, as previously thought. Combination therapy with imipenem and ampicillin could therefore be active against E. faecium strains having the dual capacity to manufacture peptidoglycan with transpeptidases of the LD- and DD-specificities. 相似文献
78.
Latijnhouwers M Gillespie T Boevink P Kriechbaumer V Hawes C Carvalho CM 《Journal of experimental botany》2007,58(15-16):4373-4386
Golgins are large coiled-coil proteins that play a role in tethering of vesicles to Golgi membranes and in maintaining the overall structure of the Golgi apparatus. Six Arabidopsis proteins with the structural characteristics of golgins were isolated and shown to locate to Golgi stacks when fused to GFP. Two of these golgin candidates (GC1 and GC2) possess C-terminal transmembrane (TM) domains with similarity to the TM domain of human golgin-84. The C-termini of two others (GC3/GDAP1 and GC4) contain conserved GRAB and GA1 domains that are also found in yeast Rud3p and human GMAP210. GC5 shares similarity with yeast Sgm1p and human TMF and GC6 with yeast Uso1p and human p115. When fused to GFP, the C-terminal domains of AtCASP and GC1 to GC6 localized to the Golgi, showing that they contain Golgi localization motifs. The N-termini, on the other hand, label the cytosol or nucleus. Immuno-gold labelling and co-expression with the cis Golgi Q-SNARE Memb11 resulted in a more detailed picture of the sub-Golgi location of some of these putative golgins. Using two independent assays it is further demonstrated that the interaction between GC5, the TMF homologue, and the Rab6 homologues is conserved in plants. 相似文献
79.
NPY regulates human endocardial endothelial cell function 总被引:1,自引:0,他引:1
Growing evidence suggests that endocardial endothelial cells (EECs) may play an important role in the regulation of cardiac function by releasing several cardioactive factors such as endothelin-1 (ET-1), Angiotensin II (Ang II) and nitric oxide (NO). In our laboratory, we demonstrated that similar to ET-1, EECs do possess different types of NPY receptors, specifically Y(1) and Y(2) receptors. Furthermore, activation of these receptors was found to increase the steady-state level of intracellular free Ca(2+) in EECs and the frequency of beating of cardiomyocytes. In addition, NPY was also found to be present in EECs, and an increase of steady-state intracellular free Ca(2+) induced the release of this peptide from these cells. Thus, similar to ET-1, NPY seems to be released from EECs and this peptide seems to regulate excitation-secretion of these cells as well as excitation-contraction coupling of ventricular cardiomyocytes. 相似文献
80.