全文获取类型
收费全文 | 1371篇 |
免费 | 73篇 |
出版年
2023年 | 3篇 |
2022年 | 16篇 |
2021年 | 27篇 |
2020年 | 12篇 |
2019年 | 16篇 |
2018年 | 15篇 |
2017年 | 17篇 |
2016年 | 32篇 |
2015年 | 40篇 |
2014年 | 69篇 |
2013年 | 69篇 |
2012年 | 85篇 |
2011年 | 115篇 |
2010年 | 69篇 |
2009年 | 48篇 |
2008年 | 110篇 |
2007年 | 95篇 |
2006年 | 85篇 |
2005年 | 81篇 |
2004年 | 77篇 |
2003年 | 87篇 |
2002年 | 76篇 |
2001年 | 16篇 |
2000年 | 16篇 |
1999年 | 11篇 |
1998年 | 19篇 |
1997年 | 5篇 |
1996年 | 15篇 |
1995年 | 14篇 |
1994年 | 8篇 |
1993年 | 14篇 |
1992年 | 11篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 6篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1972年 | 2篇 |
1967年 | 1篇 |
1965年 | 2篇 |
排序方式: 共有1444条查询结果,搜索用时 31 毫秒
991.
992.
Hashimoto M Kanda M Ikeno K Hayashi Y Nakamura T Ogawa Y Fukumitsu H Nomoto H Furukawa S 《Bioscience, biotechnology, and biochemistry》2005,69(4):800-805
Royal jelly (RJ) is known to have a variety of biological activities toward various types of cells and tissues of animal models, but nothing is known about its effect on brain functions. Hence, we examined the effect of oral administration of RJ on the mRNA expression of various neurotrophic factors, their receptors, and neural cell markers in the mouse brain. Our results revealed that RJ selectively facilitates the mRNA expression of glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor acting in the brain, and neurofilament H, a specific marker predominantly found in neuronal axons, in the adult mouse hippocampus. These observations suggest that RJ shows neurotrophic effects on the mature brain via stimulation of GDNF production, and that enhanced expression of neurofilament H mRNA is involved in events subsequently caused by GDNF. RJ may play neurotrophic and/or neuroprotective roles in the adult brain through GDNF. 相似文献
993.
994.
Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing dipeptides and is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics. The crystal structures of the saccharide-trimmed enzyme are determined as unliganded and inhibitor-liganded forms. They are informative for designing new antibiotics that are not hydrolyzed by this enzyme. The active site in each of the (alpha/beta)(8) barrel subunits of the homodimeric molecule is composed of binuclear zinc ions bridged by the Glu125 side-chain located at the bottom of the barrel, and it faces toward the microvillar membrane of a kidney tubule. A dipeptidyl moiety of the therapeutically used cilastatin inhibitor is fully accommodated in the active-site pocket, which is small enough for precise recognition of dipeptide substrates. The barrel and active-site architectures utilizing catalytic metal ions exhibit unexpected similarities to those of the murine adenosine deaminase and the catalytic domain of the bacterial urease. 相似文献
995.
Hidaka M Fushinobu S Ohtsu N Motoshima H Matsuzawa H Shoun H Wakagi T 《Journal of molecular biology》2002,322(1):79-91
The beta-galactosidase from an extreme thermophile, Thermus thermophilus A4 (A4-beta-Gal), is thermostable and belongs to the glycoside hydrolase family 42 (GH-42). As the first known structures of a GH-42 enzyme, we determined the crystal structures of free and galactose-bound A4-beta-Gal at 1.6A and 2.2A resolution, respectively. A4-beta-Gal forms a homotrimeric structure resembling a flowerpot. Each monomer has an active site located inside a large central tunnel. The N-terminal domain of A4-beta-Gal has a TIM barrel fold, as predicted from hydrophobic cluster analysis. The putative catalytic residues of A4-beta-Gal (Glu141 and Glu312) superimpose well with the catalytic residues of Escherichia coli beta-galactosidase. The environment around the catalytic nucleophile (Glu312) is similar to that in the case of E.coli beta-galactosidase, but the recognition mechanism for a substrate is different. Trp182 of the next subunit of the trimer constitutes a part of the active-site pocket, indicating that the trimeric structure is essential for the enzyme activity. Structural comparison with other glycoside hydrolases revealed that many features of the 4/7 superfamily are conserved in the A4-beta-Gal structure. On the basis of the results of 1H NMR spectroscopy, A4-beta-Gal was determined to be a "retaining" enzyme. Interestingly, the active site was similar with those of retaining enzymes, but the overall fold of the TIM barrel domain was very similar to that of an inverting enzyme, beta-amylase. 相似文献
996.
Naito E Ito M Yokota I Saijo T Matsuda J Ogawa Y Kitamura S Takada E Horii Y Kuroda Y 《Biochimica et biophysica acta》2002,1588(1):79-84
The human pyruvate dehydrogenase complex (PDHC) catalyzes the thiamine-dependent decarboxylation of pyruvate. Thiamine treatment is very effective for some patients with PDHC deficiency. Among these patients, five mutations of the pyruvate dehydrogenase (E1)alpha subunit have been reported previously: H44R, R88S, G89S, R263G, and V389fs. All five mutations are in a region outside the thiamine pyrophosphate (TPP)-binding region of the E1alpha subunit.We report the biochemical and molecular analysis of two patients with clinically thiamine-responsive lactic acidemia. The PDHC activity was assayed using two different concentrations of TPP. These two patients displayed very low PDHC activity in the presence of a low (1 x 10(-4) mM) TPP concentration, but their PDHC activity significantly increased at a high (0.4 mM) TPP concentration. Therefore, the PDHC deficiency in these two patients was due to a decreased affinity of PDHC for TPP. Treatment of both patients with thiamine resulted in a reduction in the serum lactate concentration and clinical improvement, suggesting that these two patients have a thiamine-responsive PDHC deficiency. The DNA sequence of these two male patients' X-linked E1alpha subunit revealed a point mutation (F205L and L216F) within the TPP-binding region in exon 7. 相似文献
997.
998.
Differentiation of human CD8(+) T cells from a memory to memory/effector phenotype 总被引:12,自引:0,他引:12
Tomiyama H Matsuda T Takiguchi M 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(11):5538-5550
Previous studies of perforin expression and cytokine production in subsets of peripheral human CD45RA(-)CD8(+) T cells with different CD28/CD27 phenotypes showed that CD28(+)CD45RA(-)CD8(+) and CD27(+)CD45RA(-)CD8(+) T cells have characteristics of memory T cells, whereas CD28(-)CD45RA(-)CD8(+) and CD27(-)CD45RA(-)CD8(+) T cells have characteristics of both memory and effector T cells. However, the differentiation pathway from memory CD8(+) T cells into memory/effector CD8(+) T cells has not been completely clarified. We investigated this differentiation pathway using EBV- and human CMV (HCMV)-specific CD8(+) T cells. Three subsets of CD45RA(-)CD8(+) T cells were observed in both total CD8(+) T cells and EBV- or HCMV-specific CD8(+) T cells: CD27(+)CD28(+), CD27(+)CD28(-), and CD27(-)CD28(-). A significant number of the CD27(-)CD28(+) subset was observed in total CD8 T cells. However, this subset was barely detectable in EBV- or HCMV-specific CD8(+) T cells. Analysis of perforin expression and cytotoxic activity in the first three subsets suggested the following differentiation pathway: CD27(+)CD28(+)CD45RA(-)-->CD27(+)CD28(-)CD45RA(-)-->CD27(-)CD28(-)CD45RA(-). This was supported by the observation that the frequency of CCR5(+) cells and CCR7(+) cells decreased during this sequence. Analysis of CCR5 and CCR7 expression in the CD27(+)CD28(+) memory cell subset demonstrated the presence of three CCR5/CCR7 populations: CCR5(-)CCR7(+), CCR5(+)CCR7(+), and CCR5(+)CCR7(-). These findings suggested the following differentiation pathway: CD27(+)CD28(+)CD45RA(-) (CCR5(-)CCR7(+)-->CCR5(+)CCR7(+)-->CCR5(+)CCR7(-))-->CD27(+)CD28(-)CD45RA(-)-->CD27(-)CD28(-)CD45RA(-). The presence of a CD27(-)CD28(+) subset with a CCR5(+)CCR7(-) phenotype implies a specialized role for this subset in the differentiation of CD8(+) T cells. 相似文献
999.
1000.