全文获取类型
收费全文 | 281篇 |
免费 | 28篇 |
国内免费 | 1篇 |
出版年
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 8篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 8篇 |
2014年 | 9篇 |
2013年 | 10篇 |
2012年 | 15篇 |
2011年 | 11篇 |
2010年 | 15篇 |
2009年 | 13篇 |
2008年 | 14篇 |
2007年 | 15篇 |
2006年 | 11篇 |
2005年 | 8篇 |
2004年 | 9篇 |
2003年 | 14篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 10篇 |
1997年 | 2篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1967年 | 1篇 |
1961年 | 2篇 |
1960年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有310条查询结果,搜索用时 593 毫秒
131.
132.
133.
Jurriaan J Hölzenspies Willem Stoorvogel Ben Colenbrander Bernard AJ Roelen Dagmar R Gutknecht Theo van Haeften 《BMC developmental biology》2009,9(1):1-16
Background
Fibronectin 1 (FN1), a glycoprotein component of the extracellular matrix, exerts different functions during reproductive processes such as fertilisation, gastrulation and implantation. FN1 expression has been described to increase significantly from the morula towards the early blastocyst stage, suggesting that FN1 may also be involved in early blastocyst formation. By alternative splicing at 3 defined regions, different FN1 isoforms are generated, each with a unique biological function. The analysis of the alternative FN1 splicing on the one hand and the search for candidate FN1 receptors on the other hand during early bovine embryo development may reveal more about its function during bovine preimplantation embryo development. 相似文献134.
Tania Maes Sharen Provoost Ellen A Lanckacker Didier D Cataldo Jeroen AJ Vanoirbeek Benoit Nemery Kurt G Tournoy Guy F Joos 《Respiratory research》2010,11(1):1-16
Background
Nicotinic acetylcholine receptors (nAChR) have been identified on a variety of cells of the immune system and are generally considered to trigger anti-inflammatory events. In the present study, we determine the nAChR inventory of rat alveolar macrophages (AM), and investigate the cellular events evoked by stimulation with nicotine.Methods
Rat AM were isolated freshly by bronchoalveolar lavage. The expression of nAChR subunits was analyzed by RT-PCR, immunohistochemistry, and Western blotting. To evaluate function of nAChR subunits, electrophysiological recordings and measurements of intracellular calcium concentration ([Ca2+]i) were conducted.Results
Positive RT-PCR results were obtained for nAChR subunits α3, α5, α9, α10, β1, and β2, with most stable expression being noted for subunits α9, α10, β1, and β2. Notably, mRNA coding for subunit α7 which is proposed to convey the nicotinic anti-inflammatory response of macrophages from other sources than the lung was not detected. RT-PCR data were supported by immunohistochemistry on AM isolated by lavage, as well as in lung tissue sections and by Western blotting. Neither whole-cell patch clamp recordings nor measurements of [Ca2+]i revealed changes in membrane current in response to ACh and in [Ca2+]i in response to nicotine, respectively. However, nicotine (100 μM), given 2 min prior to ATP, significantly reduced the ATP-induced rise in [Ca2+]i by 30%. This effect was blocked by α-bungarotoxin and did not depend on the presence of extracellular calcium.Conclusions
Rat AM are equipped with modulatory nAChR with properties distinct from ionotropic nAChR mediating synaptic transmission in the nervous system. Their stimulation with nicotine dampens ATP-induced Ca2+-release from intracellular stores. Thus, the present study identifies the first acute receptor-mediated nicotinic effect on AM with anti-inflammatory potential. 相似文献135.
Andreas Stein Martina Knödler Markus Makowski Sandra Kühnel Stefan Nekolla Alexandra Keithahn Eliane Weidl Philip Groha Maren Schürmann Atti Saraste Rene Botnar Robert AJ Oostendorp Ilka Ott 《BMC cardiovascular disorders》2010,10(1):43
Background
Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI.Methods and Results
In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone.Conclusion
Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.136.
Evolution of Novel O-methyltransferases from the Vanilla planifolia Caffeic Acid O-methyltransferase
Li HM Rotter D Hartman TG Pak FE Havkin-Frenkel D Belanger FC 《Plant molecular biology》2006,61(3):537-552
The biosynthesis of many plant secondary compounds involves the methylation of one or more hydroxyl groups, catalyzed by O-methyltransferases (OMTs). Here, we report the characterization of two OMTs, Van OMT-2 and Van OMT-3, from the orchid Vanilla planifolia Andrews. These enzymes catalyze the methylation of a single outer hydroxyl group in substrates possessing a 1,2,3-trihydroxybenzene
moiety, such as methyl gallate and myricetin. This is a substrate requirement not previously reported for any OMTs. Based
on sequence analysis these enzymes are most similar to caffeic acid O-methyltransferases (COMTs), but they have negligible activity with typical COMT substrates. Seven of 12 conserved substrate-binding
residues in COMTs are altered in Van OMT-2 and Van OMT-3. Phylogenetic analysis of the sequences suggests that Van OMT-2 and
Van OMT-3 evolved from the V. planifolia COMT. These V. planifolia OMTs are new instances of COMT-like enzymes with novel substrate preferences. 相似文献
137.
Spatial and temporal expression of surfactant proteins in hyperoxia-induced neonatal rat lung injury
Simone AJ ter Horst Margot Fijlstra Sujata Sengupta Frans J Walther Gerry TM Wagenaar 《BMC pulmonary medicine》2006,6(1):1-11
Background
Although personal cigarette smoking is the most important cause and modulator of chronic obstructive pulmonary disease (COPD), secondhand smoke (SHS) exposure could influence the course of the disease. Despite the importance of this question, the impact of SHS exposure on COPD health outcomes remains unknown.Methods
We used data from two waves of a population-based multiwave U.S. cohort study of adults with COPD. 77 non-smoking respondents with a diagnosis of COPD completed direct SHS monitoring based on urine cotinine and a personal badge that measures nicotine. We evaluated the longitudinal impact of SHS exposure on validated measures of COPD severity, physical health status, quality of life (QOL), and dyspnea measured at one year follow-up.Results
The highest level of SHS exposure, as measured by urine cotinine, was cross-sectionally associated with poorer COPD severity (mean score increment 4.7 pts; 95% CI 0.6 to 8.9) and dyspnea (1.0 pts; 95% CI 0.4 to 1.7) after controlling for covariates. In longitudinal analysis, the highest level of baseline cotinine was associated with worse COPD severity (4.7 points; 95% CI -0.1 to 9.4; p = 0.054), disease-specific QOL (2.9 pts; -0.16 to 5.9; p = 0.063), and dyspnea (0.9 pts; 95% CI 0.2 to 1.6 pts; p < 0.05), although the confidence intervals did not always exclude the no effect level.Conclusion
Directly measured SHS exposure appears to adversely influence health outcomes in COPD, independent of personal smoking. Because SHS is a modifiable risk factor, clinicians should assess SHS exposure in their patients and counsel its avoidance. In public health terms, the effects of SHS exposure on this vulnerable subpopulation provide a further rationale for laws prohibiting public smoking. 相似文献138.
Le Bourdonnec B Goodman AJ Michaut M Ye HF Graczyk TM Belanger S DeHaven RN Dolle RE 《Bioorganic & medicinal chemistry letters》2006,16(4):864-868
Structure-activity relationships at the 2alpha-position of the piperidine ring of the trans-4,5-dimethyl-4-(3-hydroxyphenyl)piperidine mu-opioid antagonist series were investigated. This study showed that only small linear alkyl groups (methyl, propyl) are tolerated at the 2alpha-position of the piperidine ring of this series. 相似文献
139.