全文获取类型
收费全文 | 289篇 |
免费 | 27篇 |
专业分类
316篇 |
出版年
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 3篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 10篇 |
2013年 | 9篇 |
2012年 | 11篇 |
2011年 | 12篇 |
2010年 | 14篇 |
2009年 | 8篇 |
2008年 | 22篇 |
2007年 | 17篇 |
2006年 | 13篇 |
2005年 | 12篇 |
2004年 | 19篇 |
2003年 | 16篇 |
2002年 | 9篇 |
2001年 | 13篇 |
2000年 | 10篇 |
1999年 | 5篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 6篇 |
1988年 | 6篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 9篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1958年 | 1篇 |
排序方式: 共有316条查询结果,搜索用时 0 毫秒
51.
Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The
repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently
diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted
to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes
and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder
may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of
extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical
aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate
with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major
histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune
B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize
the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies
in normal individuals. 相似文献
52.
EFFECTS OF HUMAN ACTIVITIES ON STRUCTURE AND COMPOSITION OF WOODY SPECIES OF THE NOKREK BIOSPHERE RESERVE OF MEGHALAYA,NORTHEAST INDIA 下载免费PDF全文
Aims Our study was conducted in the Nokrek Biosphere Reserve (NBR) in the Garo hills districts of Meghalaya, Northeast India. Our aim was to assess the effects of human activities on plant diversity,population structure and regeneration.Methods We selected a representative 1.2 hm2 stand in both the core and buffer zones of NBR. Structure and composition were determined by randomly sampling square quadrats, population structure was assessed by determining age structure, and regeneration was assessed by measuring densities of seedling, sapling and adult trees.Important findings More woody species were recorded from the core zone than the buffer zone (87 vs. 81 species), and there were a large number of tropical, temperate, and Sino-Himalayan, Burma-Malaysian and Malayan elements, primitive families and primitive genera. The trees were distributed in three distinct strata,canopy, subcanopy and sapling. Subcanopy and sapling layers had the highest species richness (81% -88% ). Lauraceae and Euphorbiaceae were the dominant families in terms of the number of species, and a large number of families were represented by single species. Most woody species (57 % - 79 % ) were contagiously distributed and had low frequency ( < 20% ). Although stand density was high in the buffer zone, its basal area was low compared to the stand in the core zone. Low similarity and high β-diversity indicate marked differences in species composition of the stands. Shannon diversity index was high in both the stands, while Simpson dominance index was low. The diameter-class distribution for dominant species revealed that the most had a large number of young individuals in their populations. Preponderance of tree seedlings, followed by a steep decline in population density of saplings and adult trees, indicated that the seedling to sapling stage was the most critical in the life cycle of the tree populations. Most species (42 % - 48 % ) had no regeneration,25 % - 35 % had good/fair regeneration, and the rest had poor regeneration or reoccurred as immigrants. 相似文献
53.
54.
SecA, an essential component of the secretory machinery of Escherichia coli, exists as homodimer. 总被引:5,自引:0,他引:5
M Akita A Shinkai S Matsuyama S Mizushima 《Biochemical and biophysical research communications》1991,174(1):211-216
Size exclusion chromatography of the cytosolic fraction of SecA-overproducing cells of Escherichia coli suggested that SecA, an essential component of the secretory machinery, exists as an oligomer. The subunit structure of SecA was then studied using a purified specimen. Estimation of the molecular mass by means of ultracentrifugation and chemical crosslinking analysis revealed that SecA exists as a homodimer. The purified SecA was denatured in 6 M guanidine-HCl and renatured to a dimer, which was fully active in terms of translocation, even in the presence of 1 mM dithiothreitol. It is suggested that the dimeric structure is not critically maintained by disulfide bonding between the two subunits, each of which contains four cysteine residues. 相似文献
55.
In vivo effect of a TLR5 SNP (C1205T) on Salmonella enterica serovar Typhimurium infection in weaned,specific pathogen‐free Landrace piglets 下载免费PDF全文
Yoshihiro Muneta Nobuo Arai Yoko Yakabe Masahiro Eguchi Tomoyuki Shibahara Akiko Sakuma Hiroki Shinkai Hirohide Uenishi Kensuke Hirose Masato Akiba 《Microbiology and immunology》2018,62(6):380-387
56.
We investigated the enhancement of cytokine expression by heat treatment in transiently transfected glioma cells. The cells
were transfected with plasmid bearing the interferon (IFN)-β gene under control of the MMTV promoter, which is inducible by
glucocorticoid (dexamethasone). Then magnetite particles (10 nm diameter) as intracellular heating material were incorporated
to the cells as the form of magnetoliposome. After 5 hours of incorporation, alternative magnetic field (384Oe, 118kHz) was
applied for intracellular heating. IFN-β secreted in the medium was assayed and its concentration was compared to the extracellular
heating induced expression, both in the presence and absence of dexamethasone. Higher IFN-β concentration was detected in
intracellular heating even at lower temperature, 39 °C, than 43 °C in extracellular heating. The IFN-β expression level reached
in the presence of dexamethasone was about three times higher than in the absence of inducer. In intracellular heating of
60 min, the surviving cell number reduced until 20%.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
57.
Osmoregulatory expression of porin genes in Escherichia coli: a comparative study on strains B and K-12 总被引:1,自引:0,他引:1
Takeshi Mizuno Akeo Shinkai Kenji Matsui Shoji Mizushima 《FEMS microbiology letters》1990,68(3):289-294
Escherichia coli K-12 produces both the OmpF and OmpC porins, the relative amounts of which in the outer membrane are affected in a reciprocal manner by the osmolarity of the growth medium. In contrast, E. coli B produces only the OmpF porin, regardless of the medium osmolarity. In this study, it was revealed that there is an extensive deletion within the ompC locus of the E. coli B chromosome. Cloning and nucleotide sequencing of the regulatory gene, ompR , of E. coli B revealed that there are two amino acid alterations (Lys-6 to Asn and Ala-130 to Thr) in the amino acid sequence of the OmpR protein, as compared with that of E. coli K-12. It is suggested that these particular amino acid alterations are responsible for the constitutive expression of the ompF gene observed in E. coli B. 相似文献
58.
59.
M Aoyagi N Fukai H Sakamoto T Shinkai Y Matsushima M Yamamoto K Yamamoto 《Journal of cellular physiology》1991,147(2):191-198
Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. The etiology is unknown. We examined cultured arterial smooth muscle cells (SMC) from scalp arteries of five patients with moyamoya disease. In this study we investigated the responsiveness of the cells in culture to serum mitogens including platelet-derived growth factor (PDGF), a major mitogen of SMC, and compared the response to that of cells derived from age-matched control patients. SMC from patients with moyamoya disease proliferated less rapidly in a medium with 15% serum than did control SMC and responded poorly to the addition of PDGF to 5% serum. PDGF alone did not stimulate SMC in a quiescent state to initiate DNA synthesis in moyamoya disease, without serum factors other than bovine serum albumin, though it significantly stimulated the controls. Simultaneous additions of epidermal growth factor, insulin-like growth factor-I, and PDGF stimulated initiation of DNA synthesis in cells from moyamoya disease, but not as much as PDGF alone did in the controls. Although direct correlations with the pathogenesis of the disease remain to be clarified, the results indicate altered interrelations between serum factors and the cellular responses in vessels of moyamoya disease. 相似文献
60.
Interactions between SecA and cellular components involved in the translocation of secretory proteins across the cytoplasmic membrane of Escherichia coli were studied by examining changes in the sensitivity of SecA to staphylococcal protease V8. In the presence of ATP, the amino-terminal 95-kDa portion of the SecA molecule became highly resistant to V8 digestion. Adenosine 5'-(gamma-thio)triphosphate (ATP gamma S) and ADP were as effective as ATP. For the effect, ATP could be partly replaced by CTP and UTP, but not GTP, as in the case of the protein translocation reaction. In the presence of proOmpA, a presecretory protein, on the other hand, SecA became more sensitive to V8 digestion. The signal peptide region was involved in this effect. The V8-digestion profile in the presence of both proOmpA and ATP or ADP was the same as that in the presence of proOmpA alone. Consistently, proOmpA-induced discharge of ADP or ATP gamma S from SecA was observed by means of flow dialysis. SecA-deprived everted membrane vesicles and an E. coli phospholipid mixture were also effective in making SecA more sensitive to V8 digestion. Among the phospholipids, phosphatidylglycerol and cardiolipin were effective, whereas phosphatidylethanolamine was not. It is suggested that SecA directly interacts with these cellular components and the interactions result in changes in the conformation of SecA. The physiological significance of such interactions in protein secretion is discussed. 相似文献