全文获取类型
收费全文 | 337篇 |
免费 | 26篇 |
专业分类
363篇 |
出版年
2024年 | 3篇 |
2022年 | 5篇 |
2021年 | 8篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 11篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 9篇 |
2014年 | 11篇 |
2013年 | 19篇 |
2012年 | 28篇 |
2011年 | 29篇 |
2010年 | 14篇 |
2009年 | 17篇 |
2008年 | 10篇 |
2007年 | 14篇 |
2006年 | 18篇 |
2005年 | 15篇 |
2004年 | 16篇 |
2003年 | 17篇 |
2002年 | 19篇 |
2001年 | 3篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1987年 | 7篇 |
1986年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 6篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1967年 | 2篇 |
1965年 | 3篇 |
1964年 | 2篇 |
排序方式: 共有363条查询结果,搜索用时 15 毫秒
331.
Asha GS Indira M 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2004,137(2):109-114
Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism. 相似文献
332.
Posttranslational modifications, such as the deimination of arginine to citrulline by peptidyl arginine deiminase (PAD4), change protein structure and function. For autoantigens, covalent modifications represent a mechanism to sidestep tolerance and stimulate autoimmunity. To examine conditions leading to histone deimination in neutrophils, we used Abs that detect citrullines in the N terminus of histone H3. Deimination was investigated in human neutrophils and HL-60 cells differentiated into granulocytes. We observed rapid and robust H3 deimination in HL-60 cells exposed to LPS, TNF, lipoteichoic acid, f-MLP, or hydrogen peroxide, which are stimuli that activate neutrophils. Importantly, we also observed H3 deimination in human neutrophils exposed to these stimuli. Citrullinated histones were identified as components of extracellular chromatin traps (NETs) produced by degranulating neutrophils. In contrast, apoptosis proceeded without detectable H3 deimination in HL-60 cells exposed to staurosporine or camptothecin. We conclude that histone deimination in neutrophils is induced in response to inflammatory stimuli and not by treatments that induce apoptosis. Our results further suggest that deiminated histone H3, a covalently modified form of a prominent nuclear autoantigen, is released to the extracellular space as part of the neutrophil response to infections. The possible association of a modified autoantigen with microbial components could, in predisposed individuals, increase the risk of autoimmunity. 相似文献
333.
Grauke LJ Kudva IT Yoon JW Hunt CW Williams CJ Hovde CJ 《Applied and environmental microbiology》2002,68(5):2269-2277
Experimentally inoculated sheep and cattle were used as models of natural ruminant infection to investigate the pattern of Escherichia coli O157:H7 shedding and gastrointestinal tract (GIT) location. Eighteen forage-fed cattle were orally inoculated with E. coli O157:H7, and fecal samples were cultured for the bacteria. Three distinct patterns of shedding were observed: 1 month, 1 week, and 2 months or more. Similar patterns were confirmed among 29 forage-fed sheep and four cannulated steers. To identify the GIT location of E. coli O157:H7, sheep were sacrificed at weekly intervals postinoculation and tissue and digesta cultures were taken from the rumen, abomasum, duodenum, lower ileum, cecum, ascending colon, descending colon, and rectum. E. coli O157:H7 was most prevalent in the lower GIT digesta, specifically the cecum, colon, and feces. The bacteria were only inconsistently cultured from tissue samples and only during the first week postinoculation. These results were supported in studies of four Angus steers with cannulae inserted into both the rumen and duodenum. After the steers were inoculated, ruminal, duodenal, and fecal samples were cultured periodically over the course of the infection. The predominant location of E. coli O157:H7 persistence was the lower GIT. E. coli O157:H7 was rarely cultured from the rumen or duodenum after the first week postinoculation, and this did not predict if animals went on to shed the bacteria for 1 week or 1 month. These findings suggest the colon as the site for E. coli O157:H7 persistence and proliferation in mature ruminant animals. 相似文献
334.
Luke J. Grauke Indira T. Kudva Jang Won Yoon Carl W. Hunt Christopher J. Williams Carolyn J. Hovde 《Applied microbiology》2002,68(5):2269-2277
Experimentally inoculated sheep and cattle were used as models of natural ruminant infection to investigate the pattern of Escherichia coli O157:H7 shedding and gastrointestinal tract (GIT) location. Eighteen forage-fed cattle were orally inoculated with E. coli O157:H7, and fecal samples were cultured for the bacteria. Three distinct patterns of shedding were observed: 1 month, 1 week, and 2 months or more. Similar patterns were confirmed among 29 forage-fed sheep and four cannulated steers. To identify the GIT location of E. coli O157:H7, sheep were sacrificed at weekly intervals postinoculation and tissue and digesta cultures were taken from the rumen, abomasum, duodenum, lower ileum, cecum, ascending colon, descending colon, and rectum. E. coli O157:H7 was most prevalent in the lower GIT digesta, specifically the cecum, colon, and feces. The bacteria were only inconsistently cultured from tissue samples and only during the first week postinoculation. These results were supported in studies of four Angus steers with cannulae inserted into both the rumen and duodenum. After the steers were inoculated, ruminal, duodenal, and fecal samples were cultured periodically over the course of the infection. The predominant location of E. coli O157:H7 persistence was the lower GIT. E. coli O157:H7 was rarely cultured from the rumen or duodenum after the first week postinoculation, and this did not predict if animals went on to shed the bacteria for 1 week or 1 month. These findings suggest the colon as the site for E. coli O157:H7 persistence and proliferation in mature ruminant animals. 相似文献
335.
M Moorthy P Samuel JV Peter S Vijayakumar D Sekhar VP Verghese I Agarwal PD Moses K Ebenezer OC Abraham K Thomas P Mathews AC Mishra R Lal J Muliyil AM Abraham 《PloS one》2012,7(9):e41507
Background
The burden of the pandemic (H1N1) 2009 influenza might be underestimated if detection of the virus is mandated to diagnose infection. Using an alternate approach, we propose that a much higher pandemic burden was experienced in our institution.Methodology/Principal Findings
Consecutive patients (n = 2588) presenting to our hospital with influenza like illness (ILI) or severe acute respiratory infection (SARI) during a 1-year period (May 2009–April 2010) were prospectively recruited and tested for influenza A by real-time RT-PCR. Analysis of weekly trends showed an 11-fold increase in patients presenting with ILI/SARI during the peak pandemic period when compared with the pre-pandemic period and a significant (P<0.001) increase in SARI admissions during the pandemic period (30±15.9 admissions/week) when compared with pre-pandemic (7±2.5) and post-pandemic periods (5±3.8). However, Influenza A was detected in less than one-third of patients with ILI/SARI [699 (27.0%)]; a majority of these (557/699, 79.7%) were Pandemic (H1N1)2009 virus [A/H1N1/09]. An A/H1N1/09 positive test was correlated with shorter symptom duration prior to presentation (p = 0.03). More ILI cases tested positive for A/H1N1/09 when compared with SARI (27.4% vs. 14.6%, P = 0.037). When the entire study population was considered, A/H1N1/09 positivity was associated with lower risk of hospitalization (p<0.0001) and ICU admission (p = 0.013) suggesting mild self-limiting illness in a majority.Conclusion/Significance
Analysis of weekly trends of ILI/SARI suggest a higher burden of the pandemic attributable to A/H1N1/09 than estimates assessed by a positive PCR test alone. The study highlights methodological consideration in the estimation of burden of pandemic influenza in developing countries using hospital-based data that may help assess the impact of future outbreaks of respiratory illnesses. 相似文献336.
Chattopadhyay MB Mukherjee S Kulkarni I Vijayan V Doloi M Kanjilal N Chatterjee M 《Cancer cell international》2005,5(1):16
Combined effect of vanadium and beta-carotene on rat liver DNA-chain break and Proton induced X-ray emission (PIXE) analysis
was studied during a necrogenic dose (200 mg/kg of body weight) of Diethyl Nitrosamine (DENA) induced rat liver carcinogenesis.
Morphological and histopathological changes were observed as an end point biomarker. Supplementation of vanadium (0.5 ppm
ad libitum) in drinking water and beta-carotene in the basal diet (120 mg/Kg of body weight) were performed four weeks before DENA treatment
and continued till the end of the experiment (16 weeks). PIXE analysis revealed the restoration of near normal value of zinc,
copper, and iron, which were substantially altered when compared to carcinogen treated groups. Supplementation of both vanadium
and beta-carotene four weeks before DENA injection was found to offer significant (64.73%, P < 0.001) protection against generation
of single-strand breaks when compared with the carcinogen control counter parts. A significant stabilization of hepatic architecture
of the cells was observed as compared to carcinogen control in vanadium plus beta-carotene treated group. This study thus
suggests that vanadium, a prooxidant but potential therapeutic agent yield safe and effective pharmacological formulation
with beta-carotene, an antioxidant, in the inhibition of experimental rat hepatocarcinogenesis. 相似文献
337.
338.
Unnikrishnan I Miller S Meinke M LaPorte DC 《The Journal of biological chemistry》2003,278(29):26450-26457
GSY1 is one of the two genes encoding glycogen synthase in Saccharomyces cerevisiae. Both the GSY1 message and the protein levels increased as cells approached stationary phase. A combination of deletion analysis and site-directed mutagenesis revealed a complex promoter containing multiple positive and negative regulatory elements. Expression of GSY1 was dependent upon the presence of a TATA box and two stress response elements (STREs). Expression was repressed by Mig1, which mediates responses to glucose, and Rox1, which mediates responses to oxygen. Characterization of the GSY1 promoter also revealed a novel negative element. This element, N1, can repress expression driven by either an STRE or a heterologous element, the UAS of CYC1. Repression by N1 is dependent on the number of these elements that are present, but is independent of their orientation. N1 repressed expression when placed either upstream or downstream of the UAS, although the latter position is more effective. Gel shift analysis detected a factor that appears to bind to the N1 element. The complexity of the GSY1 promoter, which includes two STREs and three distinct negative elements, was surprising. This complexity may allow GSY1 to respond to a wide range of environmental stresses. 相似文献
339.
340.
Menon C Iyer M Prabakaran I Canter RJ Lehr SC Fraker DL 《American journal of physiology. Heart and circulatory physiology》2003,284(1):H317-H329
High-dose TNF with melphalan has significant antitumor activity in regional perfusion of the limbs and liver in human malignancies. TNF is believed to target tumor vasculature, but the precise molecular mechanism is unknown. The present study demonstrates that TNF downregulates the VEGF receptor, fetal liver kinase-1 (Flk-1), on tumor endothelium in a human melanoma xenograft model. NIH1286 human melanoma cells were transduced with a 720-bp fragment of the human VEGF(121) gene to develop well-vascularized tumors that served as an amplified system for measuring Flk-1 expression changes. We injected 5 x 10(6) cells subcutaneously, each of two distinct single cell clones (NIH1286/3 and NIH1286/15), into athymic nude mice to produce tumors approximately 10 mm in size. Each animal then received either BSA or TNF in BSA by tail vein. Tumors harvested at different time points post-TNF were analyzed for Flk-1 mRNA and protein expression. Data obtained showed that intravascular TNF downregulated Flk-1 expression in tumor endothelial cells. This effect could contribute to the antitumor activity of TNF known to target tumor vasculature. 相似文献