全文获取类型
收费全文 | 385篇 |
免费 | 53篇 |
专业分类
438篇 |
出版年
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 4篇 |
2018年 | 2篇 |
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 14篇 |
2014年 | 19篇 |
2013年 | 15篇 |
2012年 | 21篇 |
2011年 | 26篇 |
2010年 | 19篇 |
2009年 | 11篇 |
2008年 | 20篇 |
2007年 | 24篇 |
2006年 | 19篇 |
2005年 | 15篇 |
2004年 | 20篇 |
2003年 | 16篇 |
2002年 | 7篇 |
2001年 | 6篇 |
2000年 | 9篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1993年 | 7篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 3篇 |
1983年 | 8篇 |
1982年 | 11篇 |
1981年 | 5篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 4篇 |
1968年 | 3篇 |
1965年 | 2篇 |
排序方式: 共有438条查询结果,搜索用时 15 毫秒
71.
This study describes the development of aptamers as a therapy against influenza virus infection. Aptamers are oligonucleotides (like ssDNA or RNA) that are capable of binding to a variety of molecular targets with high affinity and specificity. We have studied the ssDNA aptamer BV02, which was designed to inhibit influenza infection by targeting the hemagglutinin viral protein, a protein that facilitates the first stage of the virus’ infection. While testing other aptamers and during lead optimization, we realized that the dominant characteristics that determine the aptamer’s binding to the influenza virus may not necessarily be sequence-specific, as with other known aptamers, but rather depend on general 2D structural motifs. We adopted QSAR (quantitative structure activity relationship) tool and developed computational algorithm that correlate six calculated structural and physicochemical properties to the aptamers’ binding affinity to the virus. The QSAR study provided us with a predictive tool of the binding potential of an aptamer to the influenza virus. The correlation between the calculated and actual binding was R2 = 0.702 for the training set, and R2 = 0.66 for the independent test set. Moreover, in the test set the model’s sensitivity was 89%, and the specificity was 87%, in selecting aptamers with enhanced viral binding. The most important properties that positively correlated with the aptamer’s binding were the aptamer length, 2D-loops and repeating sequences of C nucleotides. Based on the structure-activity study, we have managed to produce aptamers having viral affinity that was more than 20 times higher than that of the original BV02 aptamer. Further testing of influenza infection in cell culture and animal models yielded aptamers with 10 to 15 times greater anti-viral activity than the BV02 aptamer. Our insights concerning the mechanism of action and the structural and physicochemical properties that govern the interaction with the influenza virus are discussed. 相似文献
72.
Owuor BO Odhiambo CO Otieno WO Adhiambo C Makawiti DW Stoute JA 《Molecular medicine (Cambridge, Mass.)》2008,14(3-4):89-97
Plasmodium falciparum malaria causes 1-2 million deaths per year. Most deaths occur as a result of complications such as severe anemia and cerebral malaria (CM) (coma). Red cells of children with severe malaria-associated anemia (SMA) have acquired deficiencies in the complement regulatory proteins complement receptor 1 (CR1, CD35) and decay accelerating factor (DAF, CD55). We investigated whether these deficiencies affect the ability of erythrocytes to bind immune complexes (ICs) and regulate complement activation. We recruited 75 children with SMA (Hb < or = 6 g/dL) from the holoendemic malaria region of the Lake Victoria basin, western Kenya, and 74 age- and gender-matched uncomplicated malaria controls. In addition, we recruited 32 children with CM and 52 age- and gender-matched controls. Deficiencies in red cell CR1 and CD55 in children with SMA were accompanied by a marked decline in IC binding capacity and increased C3b deposition in vivo and ex vivo. Importantly, these changes were specific because they were not seen in red cells of children with CM or their controls. These data suggest that the declines in red cell CR1 and CD55 seen in children with SMA are of physiologic significance and may predispose erythrocytes to complement-mediated damage and phagocytosis in vivo. 相似文献
73.
74.
Zlotnik A Gruenbaum BF Mohar B Kuts R Gruenbaum SE Ohayon S Boyko M Klin Y Sheiner E Shaked G Shapira Y Teichberg VI 《Biology of reproduction》2011,84(3):581-586
The gonadal steroids estrogen and progesterone have been shown to have neuroprotective properties against various neurodegenerative conditions. Excessive concentrations of glutamate have been found to exert neurotoxic properties. We hypothesize that estrogen and progesterone provide neuroprotection by the autoregulation of blood and brain glutamate levels. Venous blood samples (10 ml) were taken from 31 men and 45 women to determine blood glutamate, estrogen, progesterone, glucose, glutamate-pyruvate transaminase (GPT), and glutamate-oxaloacetate transaminase (GOT) levels, collected on Days 1, 7, 12, and 21 of the female participants' menstrual cycle. Blood glutamate concentrations were higher in men than in women at the start of menstruation (P < 0.05). Blood glutamate levels in women decreased significantly on Days 7 (P < 0.01), 12 (P < 0.001), and 21 (P < 0.001) in comparison with blood glutamate levels on Day 1. There was a significant decrease in blood glutamate levels on Days 12 (P < 0.001) and 21 (P < 0.001) in comparison with blood glutamate levels on Day 7. Furthermore, there was an increase in blood glutamate levels on Day 21 compared with Day 12 (P < 0.05). In women, there were elevated levels of estrogen on Days 7 (P < 0.05), 12, and 21 (P < 0.001), and elevated levels of progesterone on Days 12 and 21 (P < 0.001). There were no differences between men and women with respect to blood glucose concentrations. Concentrations of GOT (P < 0.05) and GPT (P < 0.001) were significantly higher in men than in women during the entire cycle. The results of this study demonstrate that blood glutamate levels are inversely correlated to levels of plasma estrogen and progesterone. 相似文献
75.
Marcela Brissova Michael J Fowler Wendell E Nicholson Anita Chu Boaz Hirshberg David M Harlan Alvin C Powers 《The journal of histochemistry and cytochemistry》2005,53(9):1087-1097
The recent success of pancreatic islet transplantation has generated considerable enthusiasm. To better understand the quality and characteristics of human islets used for transplantation, we performed detailed analysis of islet architecture and composition using confocal laser scanning microscopy. Human islets from six separate isolations provided by three different islet isolation centers were compared with isolated mouse and non-human primate islets. As expected from histological sections of murine pancreas, in isolated murine islets alpha and delta cells resided at the periphery of the beta-cell core. However, human islets were markedly different in that alpha, beta, and delta cells were dispersed throughout the islet. This pattern of cell distribution was present in all human islet preparations and islets of various sizes and was also seen in histological sections of human pancreas. The architecture of isolated non-human primate islets was very similar to that of human islets. Using an image analysis program, we calculated the volume of alpha, beta, and delta cells. In contrast to murine islets, we found that populations of islet cell types varied considerably in human islets. The results indicate that human islets not only are quite heterogeneous in terms of cell composition but also have a substantially different architecture from widely studied murine islets. 相似文献
76.
77.
78.
79.
The Uba2 and Ufd1 proteins of Saccharomyces cerevisiae interact with poly(A) polymerase and affect the polyadenylation activity of cell extracts 总被引:2,自引:0,他引:2
Poly(A) polymerase is responsible for the addition of the adenylate tail to the 3′ ends of mRNA. Using the two-hybrid system,
we have identified two proteins which interact specifically with the Saccharomyces cerevisiae poly(A) polymerase, Pap1. Uba2 is a homolog of ubiquitin-activating (E1) enzymes and Ufd1 is a protein whose function is probably
also linked to the ubiquitin-mediated protein degradation pathway. These two proteins interact with Pap1 and with each other,
but not with eight other target proteins which were tested in the two-hybrid system. The last 115 amino acids of Uba2, which
contains an 82-amino acid region not present in previously characterized E1 enzymes, is sufficient for the interaction with
Pap1. Both Uba2 and Ufd1 can be co-immunoprecipitated from extracts with Pap1, confirming in vitro the interaction identified
by two-hybrid analysis. Depletion of Uba2 from cells produces extracts which polyadenylate precursor RNA with increased efficiency
compared to extracts from nondepleted cells, while depletion of Ufd1 yields extracts which are defective in processing. These
two proteins are not components of polyadenylation factors, and instead may have a role in regulating poly(A) polymerase activity.
Received: 6 January 1997 / Accepted: 27 February 1997 相似文献
80.