全文获取类型
收费全文 | 1553篇 |
免费 | 104篇 |
国内免费 | 2篇 |
专业分类
1659篇 |
出版年
2022年 | 7篇 |
2021年 | 8篇 |
2020年 | 7篇 |
2019年 | 11篇 |
2018年 | 13篇 |
2017年 | 22篇 |
2016年 | 28篇 |
2015年 | 36篇 |
2014年 | 48篇 |
2013年 | 94篇 |
2012年 | 80篇 |
2011年 | 94篇 |
2010年 | 64篇 |
2009年 | 41篇 |
2008年 | 52篇 |
2007年 | 97篇 |
2006年 | 83篇 |
2005年 | 78篇 |
2004年 | 101篇 |
2003年 | 80篇 |
2002年 | 67篇 |
2001年 | 38篇 |
2000年 | 24篇 |
1999年 | 25篇 |
1998年 | 19篇 |
1997年 | 23篇 |
1996年 | 23篇 |
1995年 | 23篇 |
1994年 | 31篇 |
1993年 | 20篇 |
1992年 | 24篇 |
1991年 | 22篇 |
1990年 | 31篇 |
1989年 | 9篇 |
1988年 | 23篇 |
1987年 | 21篇 |
1986年 | 9篇 |
1985年 | 21篇 |
1984年 | 17篇 |
1982年 | 11篇 |
1981年 | 16篇 |
1980年 | 7篇 |
1979年 | 12篇 |
1977年 | 14篇 |
1976年 | 11篇 |
1974年 | 7篇 |
1973年 | 9篇 |
1972年 | 8篇 |
1970年 | 9篇 |
1969年 | 6篇 |
排序方式: 共有1659条查询结果,搜索用时 15 毫秒
991.
992.
993.
994.
A novel branching enzyme of the GH-57 family in the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1 下载免费PDF全文
Branching enzyme (BE) catalyzes formation of the branch points in glycogen and amylopectin by cleavage of the alpha-1,4 linkage and its subsequent transfer to the alpha-1,6 position. We have identified a novel BE encoded by an uncharacterized open reading frame (TK1436) of the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1. TK1436 encodes a conserved protein showing similarity to members of glycoside hydrolase family 57 (GH-57 family). At the C terminus of the TK1436 protein, two copies of a helix-hairpin-helix (HhH) motif were found. TK1436 orthologs are distributed in archaea of the order Thermococcales, cyanobacteria, some actinobacteria, and a few other bacterial species. When recombinant TK1436 protein was incubated with amylose used as the substrate, a product peak was detected by high-performance anion-exchange chromatography, eluting more slowly than the substrate. Isoamylase treatment of the reaction mixture significantly increased the level of short-chain alpha-glucans, indicating that the reaction product contained many alpha-1,6 branching points. The TK1436 protein showed an optimal pH of 7.0, an optimal temperature of 70 degrees C, and thermostability up to 90 degrees C, as determined by the iodine-staining assay. These properties were the same when a protein devoid of HhH motifs (the TK1436DeltaH protein) was used. The average molecular weight of branched glucan after reaction with the TK1436DeltaH protein was over 100 times larger than that of the starting substrate. These results clearly indicate that TK1436 encodes a structurally novel BE belonging to the GH-57 family. Identification of an overlooked BE species provides new insights into glycogen biosynthesis in microorganisms. 相似文献
995.
Iwata T Kawamoto T Sasabe E Miyazaki K Fujimoto K Noshiro M Kurihara H Kato Y 《European journal of cell biology》2006,85(5):423-431
996.
997.
A novel Zinc finger protein, ZCCHC11, interacts with TIFA and modulates TLR signaling 总被引:4,自引:0,他引:4
Minoda Y Saeki K Aki D Takaki H Sanada T Koga K Kobayashi T Takaesu G Yoshimura A 《Biochemical and biophysical research communications》2006,344(3):1023-1030
Toll-like receptors (TLRs) play an important role as a sensor of microbial pathogens in the innate immune response. TLRs transmit signals through the recruitment of adaptor proteins including tumor necrosis factor-associated factor 6 (TRAF6), which mediates the activation of IkappaB kinase (IKK). TIFA (TRAF-interacting protein with a forkhead-associated (FHA) domain) has been shown to bind to TRAF6 and activate IKK by promoting the oligomerization and ubiquitin-ligase activity of TRAF6. FHA domains preferentially bind to phospho-threonine residues in their targets. Here, we identified a novel zinc finger protein, ZCCHC11, that interacts with TIFA from phosphoproteins of a macrophage cell line, RAW 264.7, by using affinity purification with GST-TIFA and mass spectrometric analysis. By a search of the EST database, we found a 200kDa full-length form (ZCCHC11L). ZCCHC11L was mostly located to the nucleus, but translocated into the cytoplasm in response to LPS and bound to TIFA. Overexpression and knockdown by siRNA indicated that ZCCHC11 functions as a negative regulator of TLR-mediated NF-kappaB activation. The N-terminal region (ZCCHC11S) including C2H2-type [corrected] Zn-finger motif was sufficient for suppression of NF-kappaB. We propose that ZCCHC11 is a unique TLR signal regulator, which interacts with TIFA after LPS treatment and suppresses the TRAF6-dependent activation of NF-kappaB. 相似文献
998.
Kimura H Mukaida M Kuwabara K Ito T Hashino K Uchida K Matsumoto K Yoshida K 《Free radical biology & medicine》2006,41(6):973-978
The lipid peroxide 4-hydroxynonenal (HNE) was measured in rat intestinal mucosa after lipopolysaccharide (LPS) injection (0.5 mg/kg, ip) by a highly sensitive time-resolved fluoroimmunoassay. HNE was increased, with a small peak at 20 min followed by a sustained elevation at 2-4 h, after injection of LPS. Immunohistochemistry demonstrated enhanced labeling with anti-IgA and anti-HNE antibodies in the plasma cells followed by diffusion of the labeled materials into the submucosal tissue after LPS injection. Immunoprecipitation with anti-IgA antibody and Western blotting with anti-HNE antibody showed that IgA is modified with HNE after LPS injection. The HNE (5 microM-5 mM) modification in vitro reduced the bactericidal activity of IgA and anti-Escherichia coli serum. The HNE modification in vitro also promoted polymerization of IgA as shown by nondenaturing gel electrophoresis. This is the first demonstration of the modification of IgA with HNE in an in vivo model of intestinal inflammation as well as in vitro effects of HNE on bactericidal activity and polymerization of IgA. These findings will help in understanding the involvement of oxidative stress in the IgA-mediated immune response exerted by plasma cells in early intestinal inflammation. 相似文献
999.
Shigemura N Nakao K Yasuo T Murata Y Yasumatsu K Nakashima A Katsukawa H Sako N Ninomiya Y 《Biochemical and biophysical research communications》2008,367(2):356-363
Gurmarin (Gur) is a peptide that selectively suppresses sweet taste responses in rodents. The inhibitory effect of Gur differs among tongue regions and mouse strains. Recent studies demonstrated that co-expression levels of genes controlling sweet receptors (T1r2/T1r3 heterodimer) versus Gα-protein, gustducin, are much lower in Gur-insensitive posterior circumvallate papillae than in Gur-sensitive anterior fungiform papillae. Here, we investigated the potential link of Gur-sensitivity with the co-expression for T1r2/T1r3 receptors and gustducin by comparing those of taste tissues of Gur-sensitive (B6, dpa congenic strains) and Gur-weakly-sensitive (BALB) strains. The results indicated that co-expression ratios among T1r2, T1r3, and gustducin in the fungiform papillae were significantly lower in Gur-weakly-sensitive BALB mice than in Gur-sensitive B6 and dpa congenic mice. This linkage between Gur-sensitivity and co-expression for T1r2/T1r3 receptors versus gustducin suggests that gustducin may be a key molecule involved in the pathway for Gur-sensitive sweet responses. 相似文献
1000.
Yamada T Komoto J Kasuya T Takata Y Ogawa H Mori H Takusagawa F 《Biochimica et biophysica acta》2008,1780(5):809-818
SDH (l-serine dehydratase, EC 4.3.1.17) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes dehydration of l-Ser/Thr to yield pyruvate/ketobutyrate and ammonia. A SDH isoform (cSDH) found in human cancer cell lines has relatively low catalytic activity in comparison with the liver enzyme (hSDH). The crystal structure of cSDH has been determined at 2.8 angstroms resolution. A PLP is covalently attached to K48 by Schiff-base linkage in the active site. The ring nitrogen of PLP is involved in a H-bonding with C309, but is apparently not protonated. Twenty-three amino residues that compose the active site surfaces were identified. The human and rat liver enzymes (hSDH and rSDH) have the same residues, while residues G72, A172, and S228 in cSDH are replaced with A66, S166, and A222, respectively, in hSDH. These residues in hSDH and cSDH were mutated to make complementary pairs of mutated enzymes, and their kinetic parameters were determined. C303 of hSDH and C309 of cSDH which are H-bonding partner of the ring nitrogen of PLP were mutated to alanine and their kinetic parameters were also determined. The crystal structures and the mutation data suggest that having a glycine at residue 72 of cSDH is the major reason for the reduction of catalytic activity of cSDH. Changing alanine to glycine at residue 72 increases the flexibility of the substrate binding-loop (71S(G/A)GN74), so that the bound substrate and PLP are not pushed deep into the active cleft. Consequently, the proton transfer rate from S(G) of C309 to N1 of the bound PLP is decreased, which determines the rate of catalytic reaction. 相似文献