全文获取类型
收费全文 | 359篇 |
免费 | 17篇 |
出版年
2022年 | 6篇 |
2021年 | 9篇 |
2020年 | 4篇 |
2019年 | 9篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 8篇 |
2015年 | 7篇 |
2014年 | 12篇 |
2013年 | 23篇 |
2012年 | 26篇 |
2011年 | 15篇 |
2010年 | 11篇 |
2009年 | 12篇 |
2008年 | 16篇 |
2007年 | 20篇 |
2006年 | 12篇 |
2005年 | 25篇 |
2004年 | 22篇 |
2003年 | 14篇 |
2002年 | 9篇 |
2001年 | 7篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 11篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 1篇 |
1985年 | 5篇 |
1984年 | 1篇 |
1983年 | 6篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1970年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有376条查询结果,搜索用时 203 毫秒
111.
112.
There is a need to develop a universal vaccine against influenza virus infection to avoid developing new formulations of a seasonal vaccine each year. Many of the vaccine strategies for a universal vaccine target strain-conserved influenza virus proteins, such as the matrix, polymerase, and nucleoproteins, rather than the surface hemagglutinin and neuraminidase proteins. In addition, non-disease-causing viral vectors are a popular choice as a delivery system for the influenza virus antigens. As a proof-of-concept, we have designed a novel influenza virus immunogen based on the NP backbone containing human T cell epitopes for M1, NS1, NP, PB1 and PA proteins (referred as NPmix) as well as a construct containing the conserved regions of influenza virus neuraminidase (N-terminal) and hemagglutinin (C-terminal) (referred as NA-HA). DNA vectors and vaccinia virus recombinants expressing NPmix (WR-NP) or both NPmix plus NA-HA (WR-flu) in the cytosol were tested in a heterologous DNA-prime/vaccinia virus-boost vaccine regimen in mice. We observed an increase in the number of influenza virus-specific IFNγ-secreting splenocytes, composed of populations marked by CD4(+) and CD8(+) T cells producing IFNγ or TNFα. Upon challenge with influenza virus, the vaccinated mice exhibited decreased viral load in the lungs and a delay in mortality. These findings suggest that DNA prime/poxvirus boost with human multi-epitope recombinant influenza virus proteins is a valid approach for a general T-cell vaccine to protect against influenza virus infection. 相似文献
113.
114.
115.
One restriction to the cultivation of common bean, Phaseolus vulgaris L., is its limited tolerance to low temperatures. In the present study, subtraction suppression hybridization was employed to enrich for stress responsive genes in both a chilling-susceptible common bean and a relatively more chilling-tolerant wild bean species, Phaseolus angustissimus. For each species, approximately 11 000 expressed sequence tags were generated. Comparative sequence analysis of the EST collection with the available annotated genome sequences of the model Fabaceae species Medicago truncatula and Glycine max identified protein homologues for approximately 65% and 80% of the Phaseolus sequences, respectively. This difference reflects the closer phylogenetic relationship between the genera Phaseolus and Glycine compared with Medicago. Annotation of the Phaseolus sequences was facilitated through this comparative analysis and indicated that several heat shock proteins, cytochrome P450s, and DNA binding factors were uniquely found among the sequences from the wild species P. angustissimus. The Phaseolus sequences have been made available on a GBrowse implementation using M. truncatula as the reference genome, providing rapid access to the sequence data and associated comparative genome data. 相似文献
116.
117.
Krishna R Prabu JR Manjunath GP Datta S Chandra NR Muniyappa K Vijayan M 《Journal of molecular biology》2007,367(4):1130-1144
Mycobacterium smegmatis RecA and its nucleotide complexes crystallize in three different, but closely related, forms characterized by specific ranges of unit cell dimensions. The six crystals reported here and five reported earlier, all grown under the same or very similar conditions, belong to these three forms, all in space group P6(1). They include one obtained by reducing relative humidity around the crystal. In all crystals, RecA monomers form filaments around a 6(1) screw axis. Thus, the c-dimension of the crystal corresponds to the pitch of the RecA filament. As reported for Escherichia coli RecA, the variation in the pitch among the three forms correlates well with the motion of the C-terminal domain of the RecA monomers with respect to the main domain. The domain motion is compatible with formation of inactive as well as active RecA filaments involving monomers with a fully ordered C domain. It does not appear to influence the movement upon nucleotide-binding of the switch residue, which is believed to provide the trigger for transmitting the effect of nucleotide binding to the DNA-binding region. Interestingly, partial dehydration of the crystal results in the movement of the residue similar to that caused by nucleotide binding. The ordering of the DNA-binding loops, which present ensembles of conformations, is also unaffected by domain motion. The conformation of loop L2 appears to depend upon nucleotide binding, presumably on account of the movement of the switch residue that forms part of the loop. The conformations of loops L1 and L2 are correlated and have implications for intermolecular communications within the RecA filament. The structures resulting from different orientations of the C domain and different conformations of the DNA-binding loops appear to represent snapshots of the RecA at different phases of activity, and provide insights into the mechanism of action of RecA. 相似文献
118.
Citrate sensing by the C4-dicarboxylate/citrate sensor kinase DcuS of Escherichia coli: binding site and conversion of DcuS to a C4-dicarboxylate- or citrate-specific sensor
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Krämer J Fischer JD Zientz E Vijayan V Griesinger C Lupas A Unden G 《Journal of bacteriology》2007,189(11):4290-4298
The histidine protein kinase DcuS of Escherichia coli senses C(4)-dicarboxylates and citrate by a periplasmic domain. The closely related sensor kinase CitA binds citrate, but no C(4)-dicarboxylates, by a homologous periplasmic domain. CitA is known to bind the three carboxylate and the hydroxyl groups of citrate by sites C1, C2, C3, and H. DcuS requires the same sites for C(4)-dicarboxylate sensing, but only C2 and C3 are highly conserved. It is shown here that sensing of citrate by DcuS required the same sites. Binding of citrate to DcuS, therefore, was similar to binding of C(4)-dicarboxylates but different from that of citrate binding in CitA. DcuS could be converted to a C(4)-dicarboxylate-specific sensor (DcuS(DC)) by mutating residues of sites C1 and C3 or of some DcuS-subtype specific residues. Mutations around site C1 aimed at increasing the size and accessibility of the site converted DcuS to a citrate-specific sensor (DcuS(Cit)). DcuS(DC) and DcuS(Cit) had complementary effector specificities and responded either to C(4)-dicarboxylates or to citrate and mesaconate. The results imply that DcuS binds citrate (similar to the C(4)-dicarboxylates) via the C(4)-dicarboxylate part of the molecule. Sites C2 and C3 are essential for binding of two carboxylic groups of citrate or of C(4)-dicarboxylates; sites C1 and H are required for other essential purposes. 相似文献
119.
Basic winged bean agglutinin binds A-blood group substance with higher affinity and B-blood group substance with lesser affinity. It does not bind the O substance. The crystal structures of the lectin, complexed with A-reactive and B-reactive di and tri saccharides, have been determined. In addition, the complexes of the lectin with fucosylated A-trisaccharides and B-trisaccharides and with a variant of the A-trisaccharide have been modeled. These structures and models provide valuable insights into the structural basis of blood group specificities. All the four carbohydrate binding loops of the lectin contribute to the primary combining site while the loop of variable length contributes to the secondary binding site. In a significant advance to the current understanding, the interactions at the secondary binding site also contribute substantially, albeit in a subtle manner, to determine the blood group specificity. Compared with the interactions of the B-trisaccharide with the lectin, the third sugar residue of the A-reactive trisacharide forms an additional hydrogen bond with a lysine residue in the variable loop. In the former, the formation of such a hydrogen bond is prevented by a shift in the orientation of third sugar resulting from an internal hydrogen bond in it. The formation of this bond is also facilitated by an interaction dependent change in the rotamer conformation of the lysyl residue of the variable loop. Thus, the difference in the interactions at the secondary site is generated by coordinated movements in the ligand as well as the protein. A comparison of the crystal structure and the model of the complex involving the variant of the A-trisaccharide results in the delineation of the relative contributions of the interactions at the primary and the secondary sites in determining blood group specificity. 相似文献
120.
Lectins are a structurally diverse group of carbohydrate recognizing proteins that are involved in various biological processes and exhibit substantial structural diversity. Interestingly, in spite of having varied carbohydrate-binding specificities, they show modest variation in their secondary and tertiary structure. However, very similar tertiary folds give rise to a range of quaternary structures by simply varying the mutual orientations of the subunits involved. The variety in the quaternary structure generates multivalency in sugar specificities among lectins along with the requisite surface topology to allow for unobstructed recognition events. 相似文献