全文获取类型
收费全文 | 716篇 |
免费 | 56篇 |
国内免费 | 1篇 |
专业分类
773篇 |
出版年
2023年 | 3篇 |
2022年 | 12篇 |
2021年 | 22篇 |
2020年 | 18篇 |
2019年 | 8篇 |
2018年 | 18篇 |
2017年 | 14篇 |
2016年 | 13篇 |
2015年 | 29篇 |
2014年 | 37篇 |
2013年 | 63篇 |
2012年 | 62篇 |
2011年 | 55篇 |
2010年 | 32篇 |
2009年 | 34篇 |
2008年 | 55篇 |
2007年 | 40篇 |
2006年 | 37篇 |
2005年 | 32篇 |
2004年 | 46篇 |
2003年 | 22篇 |
2002年 | 38篇 |
2001年 | 3篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 2篇 |
1966年 | 1篇 |
1962年 | 2篇 |
排序方式: 共有773条查询结果,搜索用时 0 毫秒
101.
Effect of sesame oil on diuretics or Beta-blockers in the modulation of blood pressure, anthropometry, lipid profile, and redox status
下载免费PDF全文
![点击此处可从《The Yale journal of biology and medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The study was undertaken to investigate the effect of sesame oil in hypertensive patients who were on antihypertensive therapy either with diuretics (hydrochlorothiazide) or ß-blockers (atenolol). Thirty-two male and 18 female patients aged 35 to 60 years old were supplied sesame oil (Idhayam gingelly oil) and instructed to use it as the only edible oil for 45 days. Blood pressure, anthropometry, lipid profile, lipid peroxidation, and enzymic and non-enzymic antioxidants were measured at baseline and after 45 days of sesame oil substitution. Substitution of sesame oil brought down systolic and diastolic blood pressure to normal. The same patients were asked to withdraw sesame oil consumption for another 45 days, and the measurements were repeated at the end of withdrawal period. Withdrawal of sesame oil substitution brought back the initial blood pressure values. A significant reduction was noted in body weight and body mass index (BMI) upon sesame oil substitution. No significant alterations were observed in lipid profile except triglycerides. Plasma levels of sodium reduced while potassium elevated upon the substitution of sesame oil. Lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) decreased while the activities of superoxide dismutase (SOD), catalase (CAT), and the levels of vitamin C, vitamin E, ß-carotene, and reduced glutathione (GSH) were increased. The results suggested that sesame oil as edible oil lowered blood pressure, decreased lipid peroxidation, and increased antioxidant status in hypertensive patients. 相似文献
102.
Joshua T. Maxwell Sankar Natesan Gregory A. Mignery 《The Journal of biological chemistry》2012,287(47):39419-39428
InsP3-mediated calcium release through the type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2) in cardiac myocytes results in the activation of associated CaMKII, thus enabling the kinase to act on downstream targets, such as histone deacetylases 4 and 5 (HDAC4 and HDAC5). The CaMKII activity also feedback modulates InsP3R2 function by direct phosphorylation and results in a dramatic decrease in the receptor-channel open probability (Po). We have identified S150 in the InsP3R2 core suppressor domain (amino acids 1–225) as the specific residue that is phosphorylated by CaMKII. Site-directed mutagenesis reveals that S150 is the CaMKII phosphorylation site responsible for modulation of channel activity. Nonphosphorylatable (S150A) and phosphomimetic (S150E) mutations were studied in planar lipid bilayers. The InsP3R2 S150A channel showed no decrease in activity when treated with CaMKII. Conversely, the phosphomimetic (S150E) channel displayed a very low Po under normal recording conditions in the absence of CaMKII (2 μm InsP3 and 250 nm [Ca2+]FREE) and mimicked a WT channel that has been phosphorylated by CaMKII. Phopho-specific antibodies demonstrate that InsP3R2 Ser-150 is phosphorylated in vivo by CaMKIIδ. The results of this study show that serine 150 of the InsP3R2 is phosphorylated by CaMKII and results in a decrease in the channel open probability. 相似文献
103.
Julie Della-Maria Muralidhar L. Hegde Daniel R. McNeill Yoshihiro Matsumoto Miaw-Sheue Tsai Tom Ellenberger David M. Wilson III Sankar Mitra Alan E. Tomkinson 《The Journal of biological chemistry》2012,287(46):39233-39244
XRCC1 plays a key role in the repair of DNA base damage and single-strand breaks. Although it has no known enzymatic activity, XRCC1 interacts with multiple DNA repair proteins and is a subunit of distinct DNA repair protein complexes. Here we used the yeast two-hybrid genetic assay to identify mutant versions of XRCC1 that are selectively defective in interacting with a single protein partner. One XRCC1 mutant, A482T, that was defective in binding to polynucleotide kinase phosphatase (PNKP) not only retained the ability to interact with partner proteins that bind to different regions of XRCC1 but also with aprataxin and aprataxin-like factor whose binding sites overlap with that of PNKP. Disruption of the interaction between PNKP and XRCC1 did not impact their initial recruitment to localized DNA damage sites but dramatically reduced their retention there. Furthermore, the interaction between PNKP and the DNA ligase IIIα-XRCC1 complex significantly increased the efficiency of reconstituted repair reactions and was required for complementation of the DNA damage sensitivity to DNA alkylation agents of xrcc1 mutant cells. Together our results reveal novel roles for the interaction between PNKP and XRCC1 in the retention of XRCC1 at DNA damage sites and in DNA alkylation damage repair. 相似文献
104.
Hassing HC Surendran RP Mooij HL Stroes ES Nieuwdorp M Dallinga-Thie GM 《Biochimica et biophysica acta》2012,1821(5):826-832
The importance of triglycerides as risk factor for CVD is currently under debate. The international guidelines do not include TG into their risk calculator despite the recent observations that plasma TG is an independent risk factor for CVD. The understanding of the pathophysiology of triglycerides opens up avenues for development of new drug targets. Hypertriglyceridemia occurs through 1. Abnormalities in hepatic VLDL production, and intestinal chylomicron synthesis 2. Dysfunctional LPL-mediated lipolysis or 3. Impaired remnant clearance. The current review will discuss new aspects in lipolysis by discussing the role of GPIHBP1 and the involvement of apolipoproteins and in the process of hepatic remnant clearance with a focus upon the role of heparin sulfate proteoglycans. Finally we will shortly discuss future perspectives for novel therapies aiming at improving triglyceride homeostasis. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. 相似文献
105.
Subramanian S 《Genetics》2012,190(4):1579-1583
Here I show a gradual decline in the proportion of deleterious nonsynonymous SNPs (nSNPs) from tip to root of the human population tree. This study reveals that up to 48% of nSNPs specific to a single genome are deleterious in nature, which underscores the abundance of deleterious polymorphisms in humans. 相似文献
106.
Kashyap M Das D Preet R Mohapatra P Satapathy SR Siddharth S Kundu CN Guchhait SK 《Bioorganic & medicinal chemistry letters》2012,22(7):2474-2479
Scaffold hybridization of several natural and synthetic anticancer leads led to the consideration of indenoindolones as potential novel anticancer agents. A series of these compounds were prepared by a diversity-feasible synthetic method. They were found to possess anticancer activities with higher potency compared to etoposide and 5-fluorouracil in kidney cancer cells (HEK 293) and low toxicity to corresponding normal cells (Vero). They exerted apoptotic effect with blocking of cell cycle at G2/M phase. 相似文献
107.
Sib Sankar Giri V. Sukumaran Nitesh Kumar Dangi 《Probiotics and antimicrobial proteins》2012,4(4):238-242
In this study, we aimed to evaluate the in vitro probiotic characteristics of three bacteria, Lactobacillus plantarum VSG3, Pseudomonas aeruginosa VSG2, and Bacillus subtilis VSG1, isolated from the gut of Labeo rohita. The bacterial isolates tolerated low pH and high bile concentrations in the fish well. The bacterial adhesion capacity to fish intestinal mucosa revealed that the three potential probiotic isolates had a significantly higher adhesion capacity compared to the pathogenic strains tested. L. plantarum VSG3 exhibited the best adhesion capacity (19.1?%) to the intestinal mucosa. Among the isolates, L. plantarum VSG3 and P. aeruginosa VSG2 showed strong antibacterial activities against fish pathogens as measured in spent culture liquids. Moreover, all the isolates were susceptible to each tested antibiotic, which ensured their inability to exhibit antibiotic-resistance properties. Considering these promising results, selected strains should be further studied to determine their probiotic effects in vivo in fish. 相似文献
108.
109.
The effects of dietary Pseudomonas aeruginosa VSG-2 supplementation on innate immunity and protection against Aeromonas hydrophila infection were evaluated in Labeo rohita. Fish were fed for 60 days with control diet or 3 experimental diets containing P. aeruginosa VSG-2 at 10(5), 10(7), and 10(9) cfu g(-l), respectively. Various innate immune parameters were examined at 30 and 60 days post-feeding. Fish were challenged with A. hydrophila 60 days post-feeding and mortalities were recorded over 10 days post-infection. Dietary supplementation of P. aeruginosa VSG-2 significantly increased serum lysozyme and alternative complement pathway (ACP) activities, phagocytosis, and respiratory burst activity in head kidney macrophages of L. rohita throughout the experimental period. Superoxide dismutase (SOD) activity significantly increased after 60 days in the groups fed diets containing 10(7) and 10(9) cfu g(-1) P aeruginosa. Serum IgM levels were significantly higher in the treatment groups than in the control group after 30 days of feeding; however, the opposite result was observed at 60 days. Moreover, fish fed diets containing 10(7) and 10(9) cfu g(-1)P. aeruginosa had significantly higher post-challenge survival rates against A. hydrophila infection. Further, P. aeruginosa VSG-2 was found to be safe for mammals. These results indicate that dietary P. aeruginosa VSG-2 supplementation at 10(7) cfu g(-1) can effectively improve innate immunity and disease resistance in L. rohita. 相似文献
110.
The ‘Manning hypothesis,’ the idea that small differences in the ratio of the lengths of the human second to fourth digits—the 2D:4D ratio—reflect differences in the level of fetal androgen exposure, has been highly influential in the biological and biobehavioral sciences. The ratio is widely used to investigate the involvement of fetal androgens in the differentiation of sexually dimorphic traits. The validity of such studies is based on the premise that individual differences in the size of the 2D:4D ratio mirror differences across individuals in developmental levels of androgen exposure in a dose-dependent manner. Despite its widespread adoption by researchers, clinical evidence has yet to confirm that individual gradation in the ratio denotes differences in testosterone action. Key support for the view that 2D:4D does, in fact, reflect fetal testosterone in a graded fashion is the finding, based on a single small-sample study, that the magnitude of 2D:4D covaries with a polymorphic repeat (CAG) sequence in exon 1 of the gene coding the androgen receptor, AR. In a larger independent sample, we reexamine this genetic association and fail to substantiate a correlation between AR CAG length and 2D:4D. Combined with other recent reports, these data question one of the fundamental pieces of evidence on which the Manning hypothesis rests and raise new issues regarding the extent to which 2D:4D is a valid reflection of differences in fetal testosterone action in normally developing individuals. 相似文献