全文获取类型
收费全文 | 658篇 |
免费 | 31篇 |
国内免费 | 1篇 |
专业分类
690篇 |
出版年
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 8篇 |
2016年 | 7篇 |
2015年 | 17篇 |
2014年 | 25篇 |
2013年 | 62篇 |
2012年 | 39篇 |
2011年 | 33篇 |
2010年 | 34篇 |
2009年 | 19篇 |
2008年 | 30篇 |
2007年 | 31篇 |
2006年 | 31篇 |
2005年 | 42篇 |
2004年 | 32篇 |
2003年 | 27篇 |
2002年 | 41篇 |
2001年 | 8篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 8篇 |
1997年 | 6篇 |
1995年 | 9篇 |
1994年 | 5篇 |
1993年 | 12篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 8篇 |
1982年 | 12篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1970年 | 2篇 |
1967年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有690条查询结果,搜索用时 0 毫秒
61.
Mitsuyoshi Ueda Naoki Kanayama Naomi Kamasawa Masako Osumi Atsuo Tanaka 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2003,1631(2):160-168
In the yeast Candida tropicalis, two thiolase isozymes, peroxisomal acetoacetyl-CoA thiolase and peroxisomal 3-ketoacyl-CoA thiolase, participate in the peroxisomal fatty acid β-oxidation system. Their individual contributions have been demonstrated in cells grown on butyrate, with C. tropicalis able to grow in the absence of either one. In the present study, a lack of peroxisomal 3-ketoacyl-CoA thiolase protein resulted in increased expression (up-regulation) of acetoacetyl-CoA thiolase and other peroxisomal proteins, whereas a lack of peroxisomal acetoacetyl-CoA thiolase produced no corresponding effect. Overexpression of the acetoacetyl-CoA thiolase gene did not suppress the up-regulation or the growth retardation on butyrate in cells without peroxisomal 3-ketoacyl-CoA thiolase, even though large amounts of the overexpressed acetoacetyl-CoA thiolase were detected in most of the peroxisomes of butyrate-grown cells. These results provide important evidence of the greater contribution of 3-ketoacyl-CoA thiolase to the peroxisomal β-oxidation system than acetoacetyl-CoA thiolase in C. tropicalis and a novel insight into the regulation of the peroxisomal β-oxidation system. 相似文献
62.
Inoue K Furukawa T Kumada T Yamada J Wang T Inoue R Fukuda A 《The Journal of biological chemistry》2012,287(25):20839-20850
GABA inhibits mature neurons and conversely excites immature neurons due to lower K(+)-Cl(-) cotransporter 2 (KCC2) expression. We observed that ectopically expressed KCC2 in embryonic cerebral cortices was not active; however, KCC2 functioned in newborns. In vitro studies revealed that taurine increased KCC2 inactivation in a phosphorylation-dependent manner. When Thr-906 and Thr-1007 residues in KCC2 were substituted with Ala (KCC2T906A/T1007A), KCC2 activity was facilitated, and the inhibitory effect of taurine was not observed. Exogenous taurine activated the with-no-lysine protein kinase 1 (WNK1) and downstream STE20/SPS1-related proline/alanine-rich kinase (SPAK)/oxidative stress response 1 (OSR1), and overexpression of active WNK1 resulted in KCC2 inhibition in the absence of taurine. Phosphorylation of SPAK was consistently higher in embryonic brains compared with that of neonatal brains and down-regulated by a taurine transporter inhibitor in vivo. Furthermore, cerebral radial migration was perturbed by a taurine-insensitive form of KCC2, KCC2T906A/T1007A, which may be regulated by WNK-SPAK/OSR1 signaling. Thus, taurine and WNK-SPAK/OSR1 signaling may contribute to embryonic neuronal Cl(-) homeostasis, which is required for normal brain development. 相似文献
63.
Xiaoliang Liu Akemi Ota Michiko Watanabe Shigeharu Ueda Atsushi Saitoh Hideo Shinagawa Atsuo Nakata Takashi Kurimura Xiaoui Wang Yu Zhao Kiyoshi Kondo Jiro Seki Shinichi Miyake Nobuo Sakato Hajime Fujio 《Microbiology and immunology》1995,39(10):775-785
We investigated the murine antibody response to recombinant p17 (rp17) of human immunodeficiency virus type 1 (HIV-1) and the human antibody response directed to p17 in HIV-1 infection. Three large peptides covering residues 12-29, 53-87 and 87-115 of p17 were synthesized. The cysteine residues 57 and 87 of peptide 53-87 were reoxidized to form a disulfide bridge. Eighteen out of 19 murine monoclonal anti-rp17 antibodies had relatively high affinities (KA = 1.9 × 105?1.4 × 108 M?1) with one of the 3 p17 peptides in the liquid phase. Each monoclonal antibody reacted only with one particular peptide and had no reactivity with the other 2 p17 peptides. All the monoclonal antibodies reacted with rp17 in the liquid phase with a reasonable degree of affinity (KA = 2.0 × 105?1.8 × 107 M?1). Four HIV-1 carrier sera, which were positive in ELISA using rp17 as the antigen, reacted positively in an ELISA using 3 p17 peptides which were used to titrate murine monoclonal antibodies. Murine monoclonal antibodies having specificity for the 3 p17 peptides stained live HIV-1-infected cells by means of indirect membrane immunofluorescence, irrespective of their specificity. This suggests that the various portions of p17 (at least 3 regions of p17) were exposed on the surface of live infected cells, probably as short polypeptide chains. 相似文献
64.
Preeclampsia is characterized by pregnancy-induced hypertension accompanied with protein urea and generalized edema. Preeclampsia develops during the second half of pregnancy and resolves postpartum promptly, implicating the placenta as a primary cause in the disorder. Normal pregnancy is associated with reductions in arterial pressure and attenuated pressor response to exogenous infused angiotensin II (ANG II). In contrast, women with preeclampsia show the similar sensitivity to the pressor effect of ANG II as do non-pregnant women. To elucidate the involvement of placental peptidases associated with renin-angiotensin systems, we determined the localization of angiotensin-converting enzyme (ACE) and aminopeptidase A (AP-A), ANG II degrading enzyme, in the placenta and compared the expression of mRNA and protein in uncomplicated and preeclamptic placenta. In addition, AP-A expression in trophoblastic cells treated with ANG II and ACE expression in HUVECs under hypoxic condition were analyzed, respectively. The expression of both peptidases in the preeclamptic placenta was significantly higher than those from uncomplicated. ACE was primarily localized to venous endothelial cells of stem villous whereas AP-A expression was recognized in the trophoblast and pericytes of fetal arterioles and venules within stem villous. Hypoxia induced ACE expression in HUVECs while both hypoxia and ANG II evoked AP-A expression in trophoblast. These results suggested that hypoxic condition in preeclampsia induces ACE activation in feto-placental unit to maintain the fetal hemodynamics and placental AP-A plays a role as a component of the barrier of ANG II between mother and fetus. 相似文献
65.
Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis 总被引:9,自引:0,他引:9
Shimada A Niwa H Tsujita K Suetsugu S Nitta K Hanawa-Suetsugu K Akasaka R Nishino Y Toyama M Chen L Liu ZJ Wang BC Yamamoto M Terada T Miyazawa A Tanaka A Sugano S Shirouzu M Nagayama K Takenawa T Yokoyama S 《Cell》2007,129(4):761-772
Pombe Cdc15 homology (PCH) proteins play an important role in a variety of actin-based processes, including clathrin-mediated endocytosis (CME). The defining feature of the PCH proteins is an evolutionarily conserved EFC/F-BAR domain for membrane association and tubulation. In the present study, we solved the crystal structures of the EFC domains of human FBP17 and CIP4. The structures revealed a gently curved helical-bundle dimer of approximately 220 A in length, which forms filaments through end-to-end interactions in the crystals. The curved EFC dimer fits a tubular membrane with an approximately 600 A diameter. We subsequently proposed a model in which the curved EFC filament drives tubulation. In fact, striation of tubular membranes was observed by phase-contrast cryo-transmission electron microscopy, and mutations that impaired filament formation also impaired membrane tubulation and cell membrane invagination. Furthermore, FBP17 is recruited to clathrin-coated pits in the late stage of CME, indicating its physiological role. 相似文献
66.
Moon YH Nam SH Kang J Kim YM Lee JH Kang HK Breton V Jun WJ Park KD Kimura A Kim D 《Applied microbiology and biotechnology》2007,77(3):559-567
Two arbutin glucosides were synthesized via the acceptor reaction of a glucansucrase from Leuconostoc mesenteroides B-1299CB with arbutin and sucrose. The glucosides were purified by Bio-gel P-2 column chromatography and high-performance
liquid chromatography, and the structures were elucidated as 4-hydroxyphenyl β-isomaltoside (arbutin-G1), 4-hydroxyphenyl
β-isomaltotrioside (arbutin-G2), according to the results of 1H, 13C, heteronuclear single-quantum coherence, 1H-1H COSY, and heteronuclear multiple-bond correlation analyses. Arbutin glucoside (4-hydroxyphenyl β-isomaltoside) exhibited
slower effects on 1,1-diphenyl-2-picrylhydrazyl radical scavenging and similar effects on tyrosinase inhibition, and increased
inhibitory effect on matrix metalloproteinase-1 production induced by UVB than arbutin.
Young Hwan Moon and Seung Hee Nam contributed equally to this work. 相似文献
67.
Crystal structure of Ufc1, the Ufm1-conjugating enzyme 总被引:2,自引:0,他引:2
Mizushima T Tatsumi K Ozaki Y Kawakami T Suzuki A Ogasahara K Komatsu M Kominami E Tanaka K Yamane T 《Biochemical and biophysical research communications》2007,362(4):1079-1084
Ubiquitin and ubiquitin-like protein-conjugating enzymes play central roles in posttranslational modification processes. The ubiquitin-fold modifier 1 (Ufm1), one of a variety of ubiquitin-like modifiers, is covalently attached to target proteins via Uba5 and Ufm1-conjugating enzyme 1 (Ufc1), which are analogous to the E1 and E2 ubiquitylation enzymes. As Ufm1-related proteins are conserved in metazoa and plants, the Ufm1 system likely plays important roles in various multicellular organisms. Herein, we report the X-ray structure of human Ufc1 determined at 1.6 A resolution. The Ufc1 structure comprises a canonical E2 domain and an additional N-terminal domain. The Uba5 binding site on Ufc1 was assigned by structural comparison of Ufc1 and Ubc12 and related mutational analyses. In addition, we show that the N-terminal unique domain of Ufc1 contributes to thermal stability. 相似文献
68.
Keiichi Nomura Ayako Ikegami Atsuo Koide Fumio Yagi 《Plant Physiology and Biochemistry》2007,45(1):15-23
The annual changes in Japanese chestnut (Castanea crenata Sieb. et Zucc.) agglutinin (CCA) were investigated by both protein and RNA blotting analyses, to clarify whether CCA has a function as storage protein. In the woody part of shoots and leaves, CCA expression was only detected at both the protein and RNA levels in May and June. In buds, the CCA protein and mRNA expressions were both restricted to April. However, the amount of accumulated CCA was too low to act as a nitrogen reserve. No expression was observed in the bark at any time point, suggesting that bark does not contain either CCA or CCA-like proteins. These results suggest that CCA may be required in young organs as a defense protein, rather than as a storage protein. In addition, CCA was not related to dormancy, unlike some other woody plant bark lectins. In contrast to CCA, a 28kDa polypeptide was observed to accumulate during dormancy. Sequence analysis indicated that this polypeptide was a glutathione transferase. After cDNA cloning, RNA blot analyses indicated that this glutathione transferase was strongly expressed in woody parts during mid-winter. In shoots, this protein represented approximately 10% of the total soluble protein content. Therefore, in Japanese chestnut trees, glutathione transferase may play a nitrogen storage role in addition to its intrinsic defensive role against stresses during dormancy. 相似文献
69.
Heme is synthesized from glycine and succinyl CoA by eight heme synthesis enzymes. Although genetic defects in any of these enzymes are known to cause severe human blood diseases, their developmental expression in mammals is unknown. In this paper, we report two zebrafish heme synthesis enzymes, uroporphyrinogen III synthase (UROS) and protoporphyrinogen oxidase (PPO) that are well conserved in comparison to their human counterparts. Both UROS and PPO formed pairs of bilateral stripes in the lateral plate mesoderm at the 15-somite stage. At 24 h post-fertilization (hpf), UROS and PPO were predominantly expressed in the intermediate cell mass (ICM) that is the major site of primitive hematopoiesis. The expression of UROS and PPO was drastically suppressed in the bloodless mutants cloche and vlad tepes/gata 1 from 15-somite to 24hpf stages, indicating that both cloche and vlad tepes/gata 1 are required for the induction and maintenance of UROS and PPO expression in the ICM. 相似文献
70.
Masato Ohtsuka Hiromi Miura Keiji Mochida Michiko Hirose Ayumi Hasegawa Atsuo Ogura Ryuta Mizutani Minoru Kimura Ayako Isotani Masahito Ikawa Masahiro Sato Channabasavaiah B Gurumurthy 《BMC genomics》2015,16(1)