全文获取类型
收费全文 | 361篇 |
免费 | 31篇 |
国内免费 | 24篇 |
出版年
2023年 | 9篇 |
2022年 | 13篇 |
2021年 | 12篇 |
2020年 | 13篇 |
2019年 | 14篇 |
2018年 | 10篇 |
2017年 | 11篇 |
2016年 | 13篇 |
2015年 | 23篇 |
2014年 | 33篇 |
2013年 | 66篇 |
2012年 | 26篇 |
2011年 | 21篇 |
2010年 | 18篇 |
2009年 | 10篇 |
2008年 | 12篇 |
2007年 | 14篇 |
2006年 | 13篇 |
2005年 | 12篇 |
2004年 | 14篇 |
2003年 | 9篇 |
2002年 | 8篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有416条查询结果,搜索用时 31 毫秒
1.
《Microbes and infection / Institut Pasteur》2015,17(2):155-162
Hand, foot, and mouth disease (HFMD) caused by multiple enterovirus infections is a serious health threat to children in the Asia–Pacific region. This article reviews progresses in the development of vaccines for HFMD and discusses the need for polyvalent HFMD vaccines for conferring broad-spectrum protection. 相似文献
2.
Yi-Ting Huang Jia-Teh Liao Li-Chen Yen Yung-Kun Chang Yi-Ling Lin Ching-Len Liao 《Journal of biomedical science》2015,22(1)
Background
To construct safer recombinant flavivirus vaccine, we exploited Japanese encephalitis virus (JEV) replicon-based platform to generate single-round infectious particles (SRIPs) that expressed heterologous neutralizing epitope SP70 derived from enterovirus-71 (EV71). Such pseudo-infectious virus particles, named SRIP-SP70, although are not genuine viable viruses, closely mimic live virus infection to elicit immune responses within one round of viral life cycle.Results
We found that, besides gaining of full protection to thwart JEV lethal challenge, female outbred ICR mice, when were immunized with SRIP-SP70 by prime-boost protocol, could not only induce SP70-specific and IgG2a predominant antibodies but also provide their newborns certain degree of protection against EV71 lethal challenge.Conclusions
Our results therefore exemplify that this vaccination strategy could indeed confer an immunized host a dual protective immunity against subsequent lethal challenge from JEV or EV71. 相似文献3.
Enterovirus 2B viroporin has been involved in membrane permeabilization processes occurring late during cell infection. Even though 2B lacks an obvious signal sequence for translocation, the presence of a Lys-based amphipathic domain suggests that this product bears the intrinsic capacity for partitioning into negatively charged cytofacial membrane surfaces. Pore formation by poliovirus 2B attached to a maltose-binding protein (MBP) has been indeed demonstrated in pure lipid vesicles, a fact supporting spontaneous insertion into and direct permeabilization of membranes. Here, biochemical evidence is presented indicating that both processes are modulated by phosphatidylinositol and phosphatidylserine, the main anionic phospholipids existing in membranes of target organelles. Insertion into lipid monolayers and partitioning into phospholipid bilayers were sustained by both phospholipids. However, MBP-2B inserted into phosphatidylserine bilayers did not promote membrane permeabilization and addition of this lipid inhibited the leakage observed in phosphatidylinositol vesicles. Mathematical modelling of pore formation in membranes containing increasing phosphatidylserine percentages was consistent with its inhibitory effect arising from a higher reversibility of MBP-2B surface aggregation. These results support that 2B insertion and pore-opening are mechanistically distinguishable events modulated by the target membrane anionic phospholipids. 相似文献
4.
5.
During senescence of flowering plants, only breakdown products derived from chlorophyll a were detected although b disappears, too (Matile et al., 1996, Plant Physiol 112: 1403–1409). We investigated the possibility of chlorophyll b reduction during dark-induced senescence of barley (Hordeum vulgare L.) leaves. Plastids isolated from senescing leaves were lysed and incubated with NADPH. We found 71-hydroxy-chlorophyll a, 71-hydroxy-chlorophyllide a, and, after incubation with Zn-pheophorbide b, also Zn-71-hydroxy-pheophorbide a, indicating activity of chlorophyll(ide) b reductase. The highest activity was found at day 2 of senescence when chlorophyll breakdown reached its highest rate. Chlorophyllase
reached its highest activity under the same conditions only at days 4–6 of senescence. Based on the chlorophyll b reductase activity of plastids at day 2.5 of senescence (=100%), the bulk of activity (83%) was found in the thylakoids and
only traces (5%) in the envelope fraction. Chlorophyll b reduction is considered to be an early and obligatory step of chlorophyll b breakdown.
Received: 22 February 1999 / Accepted: 24 March 1999 相似文献
6.
Stephen D. Dertinger Yuhchyau Chen Richard K. Miller Kelly J. Brewer Therese Smudzin Dorothea K. Torous Nikki E. Hall Kristine A. Olvany Francis G. Murante Carol R. Tometsko 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2003,542(1-2):77-87
The frequency of micronuclei (also known as Howell–Jolly bodies) in peripheral blood erythrocytes of humans is extremely low due to the efficiency with which the spleen sequesters and destroys these aberrant cells. In the past, this has precluded erythrocyte-based analyses from effectively measuring chromosome damage. In this report, we describe a high-throughput, single-laser flow cytometric system for scoring the incidence of micronucleated reticulocytes (MN-RET) in human blood. Differential staining of these cells was accomplished by combining the immunochemical reagent anti-CD71-FITC with a nucleic acid dye (propidium iodide plus RNase). The immunochemical reagent anti-CD42b-PE was also incorporated into the procedure in order to exclude platelets which can interfere with analysis. This analytical system was evaluated with blood samples from ten healthy volunteers, one splenectomized subject, as well as samples collected from nine cancer patients before and over the course of radio- or chemotherapy. The mean frequency of MN-RET observed for the healthy subjects was 0.09%. This value is nearly two orders of magnitude higher than frequencies observed in mature erythrocytes, and is approximately half the MN-RET frequency observed for the splenectomized subject (0.20%). This suggests that the spleen’s effect on micronucleated cell incidence can be minimized by restricting analyses to the youngest (CD71-positive) fraction of reticulocytes. Furthermore, MN-RET frequencies were significantly elevated in patients undergoing cancer therapy. Collectively, these data establish that micronuclei can be quantified in human peripheral blood reticulocytes with a single-laser flow cytometer, and that these measurements reflect the level of chromosome damage which has occurred in red marrow space. 相似文献
7.
《Bioorganic & medicinal chemistry》2020,28(12):115551
We describe here the design, synthesis, and evaluation of a macrocyclic peptidomimetic as a potent agent targeting enterovirus A71 (EV71). The compound has a 15-membered macrocyclic ring in a defined conformation. Yamaguchi esterification reaction was used to close the 15-membered macrocycle instead of the typical Ru-catalyzed ring-closing olefin metathesis reaction. The crystallographic characterization of the complex between this compound and its target, 3C protease from EV71, validated the design and paved the way for the generation of a new series of anti-EV71 agents. 相似文献
8.
我国分离的肠道病毒71型(SHZH03病毒株)全基因组核苷酸序列分析 总被引:22,自引:0,他引:22
对肠道病毒71型(enterovirus 71,EV71)中国(深圳)分离株SHZH03进行了全基因组(未包括多聚腺苷尾)7406个碱基的核苷酸序列测定.结果表明,SHZH03株与其它肠道病毒71型毒株相比,在编码区没有核苷酸的缺失和插入,其5′UTR和3′UTR区的长度和序列有一定的差异.核苷酸同源性比较结果表明,在P1区SHZH03株与SHZH98株、中国台湾流行株(TW2086、TW2272)的同源性较高(分别为92.5%,90.1%和87.9%),与新加坡流行株SIN5666、SIN5865及标准株MS、BrCr的同源性则在81%左右,而与Coxsackievirus A16(Cox.A16)的同源性最低(63.6%).氨基酸同源性比较结果表明,在P1区SHZH03株与Cox. A16的同源性最低,但在P2和P3区SHZH03株与Cox.A16的同源性最高.P1区的遗传进化分析表明,SHZH03株和中国台湾1998年流行的EV71毒株的亲缘关系较近,属于同一型(genogroup),而与标准株BrCr和MS的亲缘关系较远.上述结果有助于肠道病毒71型的基础研究和中国对于EV71所致疾病的预防. 相似文献
9.
Non-structural poliovirus 2B protein induces plasma membrane permeabilization and has been recently implicated in triggering apoptosis via the mitochondrial pathway. Here we describe that the pore-forming P3 peptide, based on the 2B amphipathic domain, translocates through the plasma membrane of culture cells and targets mitochondria. Cell permeabilization by P3 versions of different lengths, together with peptide uptake analyses supported an internalization mechanism dependent on P3 capacity to interact physically with lipid bilayers and establish permeating pores therein. Internalized P3 was found associated with mitochondria, but contrary to the parental 2B protein, the short peptide did not affect the morphology or cell distribution of these organelles, nor induced apoptosis. We conclude that P3 constitutes a mitochondriotropic sequence, which is however devoid of 2B pro-apoptotic activity. 相似文献
10.
Brett T. Himmler Vivien C. Pellis Sergio M. Pellis 《Journal of visualized experiments : JoVE》2013,(71)
Play fighting in the rat involves attack and defense of the nape of the neck, which if contacted, is gently nuzzled with the snout. Because the movements of one animal are countered by the actions of its partner, play fighting is a complex, dynamic interaction. This dynamic complexity raises methodological problems about what to score for experimental studies. We present a scoring schema that is sensitive to the correlated nature of the actions performed. The frequency of play fighting can be measured by counting the number of playful nape attacks occurring per unit time. However, playful defense, as it can only occur in response to attack, is necessarily a contingent measure that is best measured as a percentage (#attacks defended/total # attacks X 100%). How a particular attack is defended against can involve one of several tactics, and these are contingent on defense having taken place; consequently, the type of defense is also best expressed contingently as a percentage. Two experiments illustrate how these measurements can be used to detect the effect of brain damage on play fighting even when there is no effect on overall playfulness. That is, the schema presented here is designed to detect and evaluate changes in the content of play following an experimental treatment. 相似文献