全文获取类型
收费全文 | 57篇 |
免费 | 17篇 |
出版年
2016年 | 1篇 |
2015年 | 1篇 |
2014年 | 2篇 |
2013年 | 2篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 1篇 |
2006年 | 1篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 8篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1934年 | 1篇 |
排序方式: 共有74条查询结果,搜索用时 23 毫秒
41.
alpha 1-Proteinase inhibitors (alpha 1-PIs) are members of the serpin
superfamily of proteinase inhibitors, and are important in the maintenance
of homeostasis in a wide variety of animal taxa. Previous studies have
shown that in mice (genus Mus), evolution of alpha 1-PIs is characterized
by gene amplification, region-specific concerted evolution, and rapid
accumulation of amino acid substitutions. The latter occurs primarily in
the reactive center, which is the region of the alpha 1-PI molecule that
determines the inhibitor's specificity for target proteinases. The P1
residue within the reactive center, which is methionine in so-called
orthodox alpha 1-PIs and an amino acid other than methionine in unorthodox
alpha 1-PIs, is a primary determinant of inhibitor specificity. In the
present study, we find that the expression of mRNAs encoding unorthodox
alpha 1-PIs is polymorphic within Mus species, i.e., among individuals or
inbred strains. This is in striking contrast to mRNAs that encode orthodox
alpha 1-PIs, whose concentrations are relatively invariant. The
intraspecies variations in mRNA expression represent polymorphisms in the
structure of the alpha 1- PI gene family. The results, taken together with
previously described aspects of alpha 1-PI evolution, indicate that the
dissimilar levels of polymorphism exhibited by orthodox and unorthodox
alpha 1-PIs, which likely have distinct physiological functions, may
reflect different levels of selective constraint. The significance of this
finding to the evolution of gene families is discussed.
相似文献
42.
43.
Physical map of chromosomal and plasmid DNA comprising the genome of Leptospira interrogans. 总被引:10,自引:0,他引:10 下载免费PDF全文
R L Zuerner 《Nucleic acids research》1991,19(18):4857-4860
The size and physical structure of the Leptospira interrogans genome was characterized using contour-clamped homogenous electric field (CHEF) gel electrophoresis. The L. interrogans genome is approximately 4750 kb in size and is composed of two molecular species of DNA: a 4400 kb chromosome; and a 350 kb plasmid, pLIN1. A physical map of the chromosome was constructed with the restriction enzymes NotI and SfiI. A physical map of pLIN1 was constructed with ApaI, NotI, Sse83871, SgrAI, and SmaI. Both the L. interrogans chromosome and pLIN1 are circular. 相似文献
44.
45.
Coxiella burnetii was isolated from persistently infected fibroblast host cells by a rapid mechanical lysis technique. Macromolecular synthesis was initiated in these otherwise dormant cells by incubation at pH 4.5. The synthesis of protein proceeded for as long as 24 h. Initiation of protein synthesis in C. burnetii was dependent upon RNA synthesis. Approximately 24 species of polypeptides were synthesized, and some of these appeared to be major synthetic products. Increases in protein biomass of 15 to 30% were calculated to occur during incubation. Inhibition of DNA synthesis affected protein synthesis after 12 h of incubation. The results suggest that although these parasitic bacteria did not grow in the axenic media devised, significant biosynthetic processes occurred. 相似文献
46.
Antigen/antibody complexes can efficiently target antigen presenting cells to allow stimulation of the cellular immune response. Due to the difficulty of manufacture and their inherent instability complexes have proved inefficient cancer vaccines. However, anti-idiotypic antibodies mimicking antigens have been shown to stimulate both antibody and T cell responses. The latter are due to T cell mimotopes expressed within the complementarity-determining regions (CDRs) of antibodies that are efficiently presented to dendritic cells in vivo. Based on this observation we have designed a DNA vaccine platform called ImmunoBody™, where cytotoxic T lymphocyte (CTL) and helper T cell epitopes replace CDR regions within the framework of a human IgG1 antibody. The ImmunoBody™ expression system has a number of design features which allow for rapid production of a wide range of vaccines. The CDR regions of the heavy and light chain have been engineered to contain unique restriction endonuclease sites, which can be easily opened, and oligonucleotides encoding the T cell epitopes inserted. The variable and constant regions of the ImmunoBody™ are also flanked by restriction sites, which permit easy exchange of other IgG subtypes. Here we show a range of T cell epitopes can be inserted into the ImmunoBody™ vector and upon immunization these T cell epitopes are efficiently processed and presented to stimulate high frequency helper and CTL responses capable of anti-tumor activity.Key words: DNA vaccines, cancer vaccines, melanoma, CTL, helper T cells 相似文献
47.
S10-spc-alpha is a 17.5 kb cluster of 32 genes encoding ribosomal proteins. This locus has an unusual composition and organization in Leptospira interrogans. We demonstrate the highly conserved nature of this region among diverse Leptospira and show its utility as a phylogenetically informative region. Comparative analyses were performed by PCR using primer sets covering the whole locus. Correctly sized fragments were obtained by PCR from all L. interrogans strains tested for each primer set indicating that this locus is well conserved in this species. Few differences were detected in amplification profiles between different pathogenic species, indicating that the S10-spc-alpha locus is conserved among pathogenic Leptospira. In contrast, PCR analysis of this locus using DNA from saprophytic Leptospira species and species with an intermediate pathogenic capacity generated varied results. Sequence alignment of the S10-spc-alpha locus from two pathogenic species, L. interrogans and L. borgpetersenii, with the corresponding locus from the saprophyte L. biflexa serovar Patoc showed that genetic organization of this locus is well conserved within Leptospira. Multilocus sequence typing (MLST) of four conserved regions resulted in the construction of well-defined phylogenetic trees that help resolve questions about the interrelationships of pathogenic Leptospira. Based on the results of secY sequence analysis, we found that reliable species identification of pathogenic Leptospira is possible by comparative analysis of a 245 bp region commonly used as a target for diagnostic PCR for leptospirosis. Comparative analysis of Leptospira strains revealed that strain H6 previously classified as L. inadai actually belongs to the pathogenic species L. interrogans and that L. meyeri strain ICF phylogenetically co-localized with the pathogenic clusters. These findings demonstrate that the S10-spc-alpha locus is highly conserved throughout the genus and may be more useful in comparing evolution of the genus than loci studied previously. 相似文献
48.
49.
E?BaptesteEmail author E?Susko J?Leigh D?MacLeod RL?Charlebois WF?Doolittle 《BMC evolutionary biology》2005,5(1):33
Background
Since Darwin's Origin of Species, reconstructing the Tree of Life has been a goal of evolutionists, and tree-thinking has become a major concept of evolutionary biology. Practically, building the Tree of Life has proven to be tedious. Too few morphological characters are useful for conducting conclusive phylogenetic analyses at the highest taxonomic level. Consequently, molecular sequences (genes, proteins, and genomes) likely constitute the only useful characters for constructing a phylogeny of all life. For this reason, tree-makers expect a lot from gene comparisons. The simultaneous study of the largest number of molecular markers possible is sometimes considered to be one of the best solutions in reconstructing the genealogy of organisms. This conclusion is a direct consequence of tree-thinking: if gene inheritance conforms to a tree-like model of evolution, sampling more of these molecules will provide enough phylogenetic signal to build the Tree of Life. The selection of congruent markers is thus a fundamental step in simultaneous analysis of many genes. 相似文献50.
Rishavy MA Hallgren KW Yakubenko AV Zuerner RL Runge KW Berkner KL 《The Journal of biological chemistry》2005,280(41):34870-34877
Leptospirosis is an emerging infectious disease whose pathology includes a hemorrhagic response, and sequencing of the Leptospira interrogans genome revealed an ortholog of the vitamin K-dependent (VKD) carboxylase as one of several hemostatic proteins present in the bacterium. Until now, the VKD carboxylase was known to be present only in the animal kingdom (i.e. metazoans that include mammals, fish, snails, and insects), and this restricted distribution and high sequence similarity between metazoan and Leptospira orthologs strongly suggests that Leptospira acquired the VKD carboxylase by horizontal gene transfer. In metazoans, the VKD carboxylase is bifunctional, acting as an epoxidase that oxygenates vitamin K to a strong base and a carboxylase that uses the base to carboxylate Glu residues in VKD proteins, rendering them active in hemostasis and other physiologies. In contrast, the Leptospira ortholog showed epoxidase but not detectable carboxylase activity and divergence in a region of identity in all known metazoan VKD carboxylases that is important to Glu interaction. Furthermore, although the mammalian carboxylase is regulated so that vitamin K epoxidation does not occur unless Glu substrate is present, the Leptospira VKD epoxidase showed unfettered epoxidation in the absence of Glu substrate. Finally, human VKD protein orthologs were not detected in the L. interrogans genome. The combined data, then, suggest that Leptospira exapted the metazoan VKD carboxylase for some use other than VKD protein carboxylation, such as using the strong vitamin K base to drive a new reaction or to promote oxidative damage or depleting vitamin K to indirectly inhibit host VKD protein carboxylation. 相似文献