全文获取类型
收费全文 | 2363篇 |
免费 | 239篇 |
国内免费 | 5篇 |
出版年
2022年 | 23篇 |
2021年 | 46篇 |
2020年 | 16篇 |
2019年 | 17篇 |
2018年 | 43篇 |
2017年 | 23篇 |
2016年 | 45篇 |
2015年 | 105篇 |
2014年 | 101篇 |
2013年 | 135篇 |
2012年 | 141篇 |
2011年 | 138篇 |
2010年 | 91篇 |
2009年 | 106篇 |
2008年 | 130篇 |
2007年 | 109篇 |
2006年 | 96篇 |
2005年 | 110篇 |
2004年 | 104篇 |
2003年 | 115篇 |
2002年 | 95篇 |
2001年 | 37篇 |
2000年 | 28篇 |
1999年 | 31篇 |
1998年 | 37篇 |
1997年 | 26篇 |
1996年 | 20篇 |
1995年 | 19篇 |
1994年 | 22篇 |
1993年 | 23篇 |
1992年 | 21篇 |
1991年 | 32篇 |
1990年 | 35篇 |
1989年 | 35篇 |
1988年 | 26篇 |
1987年 | 22篇 |
1986年 | 20篇 |
1985年 | 16篇 |
1984年 | 19篇 |
1983年 | 16篇 |
1982年 | 21篇 |
1981年 | 15篇 |
1979年 | 10篇 |
1978年 | 16篇 |
1977年 | 11篇 |
1976年 | 12篇 |
1971年 | 13篇 |
1970年 | 13篇 |
1968年 | 15篇 |
1963年 | 12篇 |
排序方式: 共有2607条查询结果,搜索用时 15 毫秒
91.
Fernanda Augusta de Lima Barbosa Guterres Glaucia Regina MartinezMaria Eliane Merlin Rocha Sheila Maria Brochado Winnischofer 《Experimental cell research》2013
Recent studies demonstrated that simvastatin has antitumor properties in several types of cancer cells, mainly by inducing apoptosis and inhibiting growth. The arrest of proliferation is a feature of cellular senescence; however, the occurrence of senescence in melanoma cells upon simvastatin treatment has not been investigated until now. Our results demonstrated that exposure of human metastatic melanoma cells (WM9) to simvastatin induces a senescent phenotype, characterized by G1 arrest, positive staining for senescence-associated β-galactosidase assay, and morphological changes. Also, the main pathways leading to cell senescence were examined in simvastatin-treated human melanoma cells, and the expression levels of phospho-p53 and p21 were upregulated by simvastatin, suggesting that cell cycle regulators and DNA damage pathways are involved in the onset of senescence. Since simvastatin can act as a pro-oxidant agent, and oxidative stress may be related to senescence, we measured the intracellular ROS levels in WM9 cells upon simvastatin treatment. Interestingly, we found an increased amount of intracellular ROS in these cells, which was accompanied by elevated expression of catalase and peroxiredoxin-1. Collectively, our results demonstrated that simvastatin can induce senescence in human melanoma cells by activation of p53/p21 pathway, and that oxidative stress may be related to this process. 相似文献
92.
Sheila Unger Maria?W. Górna Antony Le?Béchec Sonia Do?Vale-Pereira Maria?Francesca Bedeschi Stefan Geiberger Giedre Grigelioniene Eva Horemuzova Faustina Lalatta Ekkehart Lausch Cinzia Magnani Sheela Nampoothiri Gen Nishimura Duccio Petrella Francisca Rojas-Ringeling Akari Utsunomiya Bernhard Zabel Sylvain Pradervand Keith Harshman Belinda Campos-Xavier Luisa Bonafé Giulio Superti-Furga Brian Stevenson Andrea Superti-Furga 《American journal of human genetics》2013,92(6):990-995
Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth. 相似文献
93.
Aspects which need to be considered when calculating pollen influx values in three sedimentary environments (pollen traps, peats and lake sediments) are reviewed. Examples of influx values (grains cm-2 year-1) in northern Fennoscandia for two arboreal taxa Betula and Pinus, calculated from these three different environments are presented. Such long term average pollen influx values can be used to indicate the presence/absence and density of the species within the vicinity of the sampling site. Contrary to expectations, conditions do exist in which numerically comparable values are obtained from all three environments. Using these pollen influx values to interpret forest and woodland history in tree-line situations, from both peats and lake sediments, a higher degree of precision can be obtained than through the more classical pollen percentage method alone. 相似文献
94.
95.
96.
Meghna Desai Penelope A. Phillips-Howard Frank O. Odhiambo Abraham Katana Peter Ouma Mary J. Hamel Jackton Omoto Sheila Macharia Annemieke van Eijk Sheila Ogwang Laurence Slutsker Kayla F. Laserson 《PloS one》2013,8(7)
Background
Pregnancy-related (PR) deaths are often a result of direct obstetric complications occurring at childbirth.Methods and Findings
To estimate the burden of and characterize risk factors for PR mortality, we evaluated deaths that occurred between 2003 and 2008 among women of childbearing age (15 to 49 years) using Health and Demographic Surveillance System data in rural western Kenya. WHO ICD definition of PR mortality was used: “the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death”. In addition, symptoms and events at the time of death were examined using the WHO verbal autopsy methodology. Deaths were categorized as either (i) directly PR: main cause of death was ascribed as obstetric, or (ii) indirectly PR: main cause of death was non-obstetric. Of 3,223 deaths in women 15 to 49 years, 249 (7.7%) were PR. One-third (34%) of these were due to direct obstetric causes, predominantly postpartum hemorrhage, abortion complications and puerperal sepsis. Two-thirds were indirect; three-quarters were attributable to human immunodeficiency virus (HIV/AIDS), malaria and tuberculosis. Significantly more women who died in lower socio-economic groups sought care from traditional birth attendants (p = 0.034), while less impoverished women were more likely to seek hospital care (p = 0.001). The PR mortality ratio over the six years was 740 (95% CI 651–838) per 100,000 live births, with no evidence of reduction over time (χ2 linear trend = 1.07; p = 0.3).Conclusions
These data supplement current scanty information on the relationship between infectious diseases and poor maternal outcomes in Africa. They indicate low uptake of maternal health interventions in women dying during pregnancy and postpartum, suggesting improved access to and increased uptake of skilled obstetric care, as well as preventive measures against HIV/AIDS, malaria and tuberculosis among all women of childbearing age may help to reduce pregnancy-related mortality. 相似文献97.
98.
Gerco den Hartog Ranajoy Chattopadhyay Amber Ablack Emily H. Hall Lindsay D. Butcher Asima Bhattacharyya Lars Eckmann Paul R. Harris Soumita Das Peter B. Ernst Sheila E. Crowe 《PLoS pathogens》2016,12(1)
Generation of reactive oxygen species (ROS) during infection is an immediate host defense leading to microbial killing. APE1 is a multifunctional protein induced by ROS and after induction, protects against ROS-mediated DNA damage. Rac1 and NAPDH oxidase (Nox1) are important contributors of ROS generation following infection and associated with gastrointestinal epithelial injury. The purpose of this study was to determine if APE1 regulates the function of Rac1 and Nox1 during oxidative stress. Gastric or colonic epithelial cells (wild-type or with suppressed APE1) were infected with Helicobacter pylori or Salmonella enterica and assessed for Rac1 and NADPH oxidase-dependent superoxide production. Rac1 and APE1 interactions were measured by co-immunoprecipitation, confocal microscopy and proximity ligation assay (PLA) in cell lines or in biopsy specimens. Significantly greater levels of ROS were produced by APE1-deficient human gastric and colonic cell lines and primary gastric epithelial cells compared to control cells after infection with either gastric or enteric pathogens. H. pylori activated Rac1 and Nox1 in all cell types, but activation was higher in APE1 suppressed cells. APE1 overexpression decreased H. pylori-induced ROS generation, Rac1 activation, and Nox1 expression. We determined that the effects of APE1 were mediated through its N-terminal lysine residues interacting with Rac1, leading to inhibition of Nox1 expression and ROS generation. APE1 is a negative regulator of oxidative stress in the gastrointestinal epithelium during bacterial infection by modulating Rac1 and Nox1. Our results implicate APE1 in novel molecular interactions that regulate early stress responses elicited by microbial infections. 相似文献
99.
100.
Sheila N. Balinda Pascale Ondoa Ekwaro A. Obuku Aletta Kliphuis Isaac Egau Michelle Bronze Lordwin Kasambula Rob Schuurman Nicole Spieker Tobias F. Rinke de Wit Cissy Kityo ART–A consortium 《PloS one》2016,11(1)