全文获取类型
收费全文 | 8933篇 |
免费 | 771篇 |
国内免费 | 1篇 |
专业分类
9705篇 |
出版年
2024年 | 12篇 |
2023年 | 39篇 |
2022年 | 109篇 |
2021年 | 228篇 |
2020年 | 113篇 |
2019年 | 152篇 |
2018年 | 188篇 |
2017年 | 161篇 |
2016年 | 292篇 |
2015年 | 469篇 |
2014年 | 508篇 |
2013年 | 546篇 |
2012年 | 775篇 |
2011年 | 736篇 |
2010年 | 459篇 |
2009年 | 423篇 |
2008年 | 569篇 |
2007年 | 569篇 |
2006年 | 532篇 |
2005年 | 535篇 |
2004年 | 491篇 |
2003年 | 458篇 |
2002年 | 430篇 |
2001年 | 73篇 |
2000年 | 50篇 |
1999年 | 104篇 |
1998年 | 111篇 |
1997年 | 71篇 |
1996年 | 56篇 |
1995年 | 58篇 |
1994年 | 47篇 |
1993年 | 51篇 |
1992年 | 40篇 |
1991年 | 31篇 |
1990年 | 38篇 |
1989年 | 26篇 |
1988年 | 28篇 |
1987年 | 18篇 |
1986年 | 16篇 |
1985年 | 15篇 |
1984年 | 18篇 |
1983年 | 12篇 |
1982年 | 11篇 |
1981年 | 11篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 2篇 |
排序方式: 共有9705条查询结果,搜索用时 15 毫秒
991.
Yiu-Wing Kam Wendy W. L. Lee Diane Simarmata Roger Le Grand Hugues Tolou Andres Merits Pierre Roques Lisa F. P. Ng 《PloS one》2014,9(4)
Chikungunya virus (CHIKV) is an Alphavirus that causes chronic and incapacitating arthralgia in humans. Although patient cohort studies have shown the production of CHIKV specific antibodies, the fine specificity of the antibody response against CHIKV is not completely defined. The macaque model of CHIKV infection was established due to limitations of clinical specimens. More importantly, its close relation to humans will allow the study of chronic infection and further identify important CHIKV targets. In this study, serum samples from CHIKV-infected macaques collected at different time-points post infection were used to characterize the antibody production pattern and kinetics. Results revealed that anti-CHIKV antibodies were neutralizing and the E2 glycoprotein, Capsid, nsP1, nsP3 and nsP4 proteins were targets of the anti-CHIKV antibody response in macaques. Furthermore, linear B-cell epitopes recognized by these anti-CHIKV antibodies were identified, and mapped to their structural localization. This characterizes the specificity of anti-CHIKV antibody response in macaques and further demonstrates the importance of the different regions in CHIKV-encoded proteins in the adaptive immune response. Information from this study provides critical knowledge that will aid in the understanding of CHIKV infection and immunity, vaccine design, and pre-clinical efficacy studies. 相似文献
992.
993.
Prosser LA Lavelle TA Fiore AE Bridges CB Reed C Jain S Dunham KM Meltzer MI 《PloS one》2011,6(7):e22308
Background
Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination.Methodology
A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted.Results
For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000–$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery.Conclusions
Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of vaccination. 相似文献994.
The effects of nutritional copper deficiency on carrageenin edema in the rat were investigated with emphasis on studying the
correlation between the degree of copper deficiency and the degree of edema. Carrageenin paw edema in both copper-sufficient
and copper-deficient groups of rats was compared after either 20, 40, or 60 d on respective diets. The degree of copper deficiency
was quantitated by analyzing total copper concentrations in a number of tissues. Other copper dependent parameters were also
determined. Results indicated that: (1) although copper sufficient rats showed relatively little change in the degree of edema,
copper-deficient rats showed a steady and significant increase in edema from d 20 to 40 to 60; (2) paw edema in copper-deficient
animals was highly and negatively correlated to the concentrations of copper in the liver; the correlation with liver Cu,Zn-superoxide
dismutase activity, however, was inconsistent; (3) paw edema was not correlated either to copper concentration in tissues
other than liver or to plasma ceruloplasmin activity; and (4) aggravation of carrageenin edema in copper-deficient animals
seemed to be mediated via an as yet unknown secondary effect of copper deficiency. 相似文献
995.
Lars Dölken Georg Malterer Florian Erhard Sheila Kothe Caroline C. Friedel Guillaume Suffert Lisa Marcinowski Natalie Motsch Stephanie Barth Michaela Beitzinger Diana Lieber Susanne M. Bailer Reinhard Hoffmann Zsolt Ruzsics Elisabeth Kremmer Sébastien Pfeffer Ralf Zimmer Ulrich H. Koszinowski Friedrich Grässer Gunter Meister Jürgen Haas 《Cell host & microbe》2010,7(4):324-334
996.
997.
998.
999.
John F. Bateman Lisa Sampurno Antonio Maurizi Shireen R. Lamand Natalie A. Sims Tegan L. Cheng Aaron Schindeler David G. Little 《Journal of cellular and molecular medicine》2019,23(3):1735-1745
Osteogenesis imperfecta (OI) is commonly caused by heterozygous type I collagen structural mutations that disturb triple helix folding and integrity. This mutant‐containing misfolded collagen accumulates in the endoplasmic reticulum (ER) and induces a form of ER stress associated with negative effects on osteoblast differentiation and maturation. Therapeutic induction of autophagy to degrade the mutant collagens could therefore be useful in ameliorating the ER stress and deleterious downstream consequences. To test this, we treated a mouse model of mild to moderate OI (α2(I) G610C) with dietary rapamycin from 3 to 8 weeks of age and effects on bone mass and mechanical properties were determined. OI bone mass and mechanics were, as previously reported, compromised compared to WT. While rapamycin treatment improved the trabecular parameters of WT and OI bones, the biomechanical deficits of OI bones were not rescued. Importantly, we show that rapamycin treatment suppressed the longitudinal and transverse growth of OI, but not WT, long bones. Our work demonstrates that dietary rapamycin offers no clinical benefit in this OI model and furthermore, the impact of rapamycin on OI bone growth could exacerbate the clinical consequences during periods of active bone growth in patients with OI caused by collagen misfolding mutations. 相似文献
1000.
Berggren PO Yang SN Murakami M Efanov AM Uhles S Köhler M Moede T Fernström A Appelskog IB Aspinwall CA Zaitsev SV Larsson O de Vargas LM Fecher-Trost C Weissgerber P Ludwig A Leibiger B Juntti-Berggren L Barker CJ Gromada J Freichel M Leibiger IB Flockerzi V 《Cell》2004,119(2):273-284
An oscillatory increase in pancreatic beta cell cytoplasmic free Ca2+ concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The role of the voltage-gated Ca2+ channel beta3 subunit in the molecular regulation of these [Ca2+]i oscillations has now been clarified by using beta3 subunit-deficient beta cells. beta3 knockout mice showed a more efficient glucose homeostasis compared to wild-type mice due to increased glucose-stimulated insulin secretion. This resulted from an increased glucose-induced [Ca2+]i oscillation frequency in beta cells lacking the beta3 subunit, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca2+ mobilization from intracellular stores. Hence, the beta3 subunit negatively modulated InsP3-induced Ca2+ release, which is not paralleled by any effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin release was manifested only at high glucose concentrations, blocking the beta3 subunit in the beta cell may constitute the basis for a novel diabetes therapy. 相似文献