全文获取类型
收费全文 | 4638篇 |
免费 | 426篇 |
国内免费 | 1篇 |
专业分类
5065篇 |
出版年
2021年 | 33篇 |
2018年 | 36篇 |
2016年 | 52篇 |
2015年 | 101篇 |
2014年 | 114篇 |
2013年 | 172篇 |
2012年 | 213篇 |
2011年 | 189篇 |
2010年 | 122篇 |
2009年 | 124篇 |
2008年 | 181篇 |
2007年 | 202篇 |
2006年 | 204篇 |
2005年 | 178篇 |
2004年 | 172篇 |
2003年 | 170篇 |
2002年 | 179篇 |
2001年 | 61篇 |
2000年 | 52篇 |
1999年 | 59篇 |
1998年 | 73篇 |
1997年 | 42篇 |
1996年 | 42篇 |
1994年 | 34篇 |
1993年 | 42篇 |
1992年 | 59篇 |
1991年 | 51篇 |
1990年 | 47篇 |
1989年 | 51篇 |
1988年 | 53篇 |
1987年 | 55篇 |
1986年 | 69篇 |
1985年 | 71篇 |
1984年 | 68篇 |
1983年 | 62篇 |
1982年 | 61篇 |
1981年 | 63篇 |
1980年 | 70篇 |
1979年 | 70篇 |
1978年 | 69篇 |
1977年 | 57篇 |
1976年 | 67篇 |
1975年 | 47篇 |
1974年 | 58篇 |
1973年 | 41篇 |
1970年 | 37篇 |
1969年 | 30篇 |
1968年 | 45篇 |
1967年 | 33篇 |
1961年 | 38篇 |
排序方式: 共有5065条查询结果,搜索用时 0 毫秒
81.
82.
Activation of a low specific activity form of DNA polymerase alpha by inositol-1,4-bisphosphate 总被引:9,自引:0,他引:9
A low activity form of DNA polymerase alpha immunoaffinity-purified from adult-derived human fibroblasts was activated by interaction with phosphatidylinositol-4-monophosphate, while a high activity form of the enzyme did not interact with phosphatidylinositol-4-monophosphate or its derivatives. Phosphatidylinositol-4-monophosphate was apparently hydrolyzed in the presence of a highly purified low activity form of DNA polymerase alpha, effecting the release of diacylglycerol and the retention of inositol-1,4-bisphosphate by the enzyme complex. The resulting inositol-1,4-bisphosphate/protein complex exhibited increased affinity of binding to DNA template/primer and increased deoxynucleotidyltransferase activity. These data indicate that inositol-1,4-bisphosphate may function as an effector molecule in the activation of a low activity form of human DNA polymerase alpha and suggest that it may function as a second messenger during the initiation of mitosis in stimulated cells. 相似文献
83.
Harrison-Lavoie KJ Michaux G Hewlett L Kaur J Hannah MJ Lui-Roberts WW Norman KE Cutler DF 《Traffic (Copenhagen, Denmark)》2006,7(6):647-662
The biogenesis of endothelial-specific Weibel-Palade bodies (WPB) is poorly understood, despite their key role in both haemostasis and inflammation. Biogenesis of specialized organelles of haemopoietic cells is often adaptor protein complex 3-dependent (AP-3-dependent), and AP-3 has previously been shown to play a role in the trafficking of both WPB membrane proteins, P-selectin and CD63. However, WPB are thought to form at the trans Golgi network (TGN), which is inconsistent with a role for AP-3, which operates in post-Golgi trafficking. We have therefore investigated in detail the mechanisms of delivery of these two membrane proteins to WPB. We find that P-selectin is recruited to forming WPB in the trans-Golgi by AP-3-independent mechanisms that use sorting information within both the cytoplasmic tail and the lumenal domain of the receptor. In contrast, CD63 is recruited to already-budded WPB by an AP-3-dependent route. These different mechanisms of recruitment lead to the presence of distinct immature and mature populations of WPB in human umbilical vein endothelial cells (HUVEC). 相似文献
84.
Genevieve G. A. Fouda Joshua D. Amos Andrew B. Wilks Justin Pollara Caroline A. Ray Anjali Chand Erika L. Kunz Brooke E. Liebl Kaylan Whitaker Angela Carville Shannon Smith Lisa Colvin David J. Pickup Herman F. Staats Glenn Overman Krissey Eutsey-Lloyd Robert Parks Haiyan Chen Celia LaBranche Susan Barnett Georgia D. Tomaras Guido Ferrari David C. Montefiori Hua-Xin Liao Norman L. Letvin Barton F. Haynes Sallie R. Permar 《Journal of virology》2013,87(12):6986-6999
We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody responses in milk, hormone-induced lactating rhesus monkeys were vaccinated with a transmitted/founder (T/F) HIV Env immunogen in a prime-boost strategy modeled after the moderately protective RV144 HIV vaccine. Lactating rhesus monkeys were intramuscularly primed with either recombinant DNA (n = 4) or modified vaccinia virus Ankara (MVA) poxvirus vector (n = 4) expressing the T/F HIV Env C.1086 and then boosted twice intramuscularly with C.1086 gp120 and the adjuvant MF59. The vaccines induced Env-binding IgG and IgA as well as neutralizing and antibody-dependent cellular cytotoxicity (ADCC) responses in plasma and milk of most vaccinated animals. Importantly, plasma neutralization titers against clade C HIV variants MW965 (P = 0.03) and CAP45 (P = 0.04) were significantly higher in MVA-primed than in DNA-primed animals. The superior systemic prime-boost regimen was then compared to a mucosal-boost regimen, in which animals were boosted twice intranasally with C.1086 gp120 and the TLR 7/8 agonist R848 following the same systemic prime. While the systemic and mucosal vaccine regimens elicited comparable levels of Env-binding IgG antibodies, mucosal immunization induced significantly stronger Env-binding IgA responses in milk (P = 0.03). However, the mucosal regimen was not as potent at inducing functional IgG responses. This study shows that systemic MVA prime followed by either intranasal or systemic protein boosts can elicit strong humoral responses in breast milk and may be a useful strategy to interrupt postnatal HIV-1 transmission. 相似文献
85.
86.
Victor Kunin Jeroen Raes J Kirk Harris John R Spear Jeffrey J Walker Natalia Ivanova Christian von Mering Brad M Bebout Norman R Pace Peer Bork Philip Hugenholtz 《Molecular systems biology》2008,4(1)
To investigate the extent of genetic stratification in structured microbial communities, we compared the metagenomes of 10 successive layers of a phylogenetically complex hypersaline mat from Guerrero Negro, Mexico. We found pronounced millimeter‐scale genetic gradients that were consistent with the physicochemical profile of the mat. Despite these gradients, all layers displayed near‐identical and acid‐shifted isoelectric point profiles due to a molecular convergence of amino‐acid usage, indicating that hypersalinity enforces an overriding selective pressure on the mat community. 相似文献
87.
Circulating ceramides are inversely associated with cardiorespiratory fitness in participants aged 54–96 years from the Baltimore Longitudinal Study of Aging 下载免费PDF全文
Elisa Fabbri An Yang Eleanor M. Simonsick Chee W. Chia Marco Zoli Norman J. Haughey Michelle M. Mielke Paul M. Coen 《Aging cell》2016,15(5):825-831
Cardiorespiratory fitness (VO2 peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO2 peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA). Individual species of ceramide were quantified by HPLC–tandem mass spectrometry. VO2 peak was measured by a graded treadmill test. We applied multiple regression models to test the associations between ceramide species and VO2 peak, while adjusting for age, sex, blood pressure, serum LDL, HDL, triglycerides, and other covariates. We found that higher levels of circulating C18:0, C20:0, C24:1 ceramides and C20:0 dihydroceramides were strongly associated with lower aerobic capacity (P < 0.001, P < 0.001, P = 0.018, and P < 0.001, respectively). The associations held true for both sexes (with men having a stronger association than women, P value for sex interaction <0.05) and were unchanged after adjusting for confounders and multiple comparison correction. Interestingly, no significant association was found for C16:0, C22:0, C24:0, C26:0, and C22:1 ceramide species, C24:0 dihydroceramide, or total ceramides. Our analysis reveals that specific long‐chain ceramides strongly associate with low cardiovascular fitness in older adults and may be implicated in the pathogenesis of low fitness with aging. Longitudinal studies are needed to further validate these associations and investigate the relationship between ceramides and health outcomes. 相似文献
88.
89.
Dale Nicholas Tian Faming Sagoo Ravjit Phillips Norman Imray Chris Roffe Christine 《Purinergic signalling》2019,15(2):237-246
Purinergic Signalling - Stroke is a leading cause of death and disability. Here, we examine whether point-of-care measurement of the purines, adenosine, inosine and hypoxanthine, which are... 相似文献
90.
Vector-borne diseases are of global importance to human and animal health. Empirical trials of effective methods to control
vectors and their pathogens can be difficult for practical, financial and ethical reasons. Here, therefore, we use a mathematical
model to predict the effectiveness of a vector-borne disease control method. As a case study, we use the tick-louping ill
virus system, where sheep are treated with acaricide in an attempt to control ticks and disease in red grouse , an economically
important game bird. We ran the model under different scenarios of sheep flock sizes, alternative host (deer) densities, acaricide
efficacies and tick burdens. The model predicted that, with very low deer densities, using sheep as tick mops can reduce the
tick population and virus prevalence. However, treatment is ineffective above a certain threshold deer density, dependent
on the comparative tick burden on sheep and deer. The model also predicted that high efficacy levels of acaricide must be
maintained for effective tick control. This study suggests that benignly managing one host species to protect another host
species from a vector and pathogen can be effective under certain conditions. It also highlights the importance of understanding
the ecological complexity of a system, in order to target control methods only under certain circumstances for maximum effectiveness. 相似文献