全文获取类型
收费全文 | 192篇 |
免费 | 14篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 5篇 |
2013年 | 5篇 |
2012年 | 8篇 |
2011年 | 6篇 |
2010年 | 7篇 |
2009年 | 18篇 |
2008年 | 13篇 |
2007年 | 14篇 |
2006年 | 14篇 |
2005年 | 10篇 |
2004年 | 13篇 |
2003年 | 17篇 |
2002年 | 6篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 5篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1986年 | 2篇 |
1984年 | 2篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有206条查询结果,搜索用时 18 毫秒
81.
Okumura T Takeuchi S Motomura W Yamada H Egashira Si S Asahi S Kanatani A Ihara M Kohgo Y 《Biochemical and biophysical research communications》2001,280(4):976-981
Orexin-A is a neuropeptide consisting of 33 amino acids with two intrachain disulfide bonds, namely Cys6-Cys12 and Cys7-Cys14, and is a potent stimulator of food consumption and gastric acid secretion. In contrast, orexin-B, a peptide containing 28 amino acids without disulfide bond, which has no stimulatory action of gastric acid. The objective of the present study was to characterize the receptor-mediated mechanism of orexin-A-induced stimulation of gastric acid secretion using orexin-A-related peptides with modification of disulfide bonds. Intracisternal injection of orexin-A, but not orexin-B or orexin-A (15-33), that does not contain both disulfide bonds stimulated gastric acid secretion in pylorus-ligated conscious rats. The ability of the stimulation of gastric acid output was less in three alanine-substituted orexin-A, [Ala(6,12)]orexin-A, [Ala(7,14)]orexin-A, and [Ala(6,7,12,14)]orexin-A, than orexin-A. Orexins-induced calcium increase was measured in CHO-K1 cells expressing OX1R or OX2R. Orexin-A induced a transient increase in [Ca(2+)]i in CHO-K1/OX1R cells in a dose-dependent manner. EC50 values for OX1R of orexin-A, orexin-B, or orexin-A (15-33) was 0.068, 0.69 or 4.1 nM, respectively, suggesting that peptides containing no disulfide bonds have lower potency for the receptor. Agonistic activity for OX1R of the three orexin-A analogues with modification of one or both disulfide bonds was significantly reduced as compared with that of orexin-A. EC50 values for OX2R of orexin-A and orexin-B was almost equal but potency for the receptor of orexin-A (15-33) and three alanine substituted orexin-A was less than that of orexin-A. A significant inverse relationship between gastric acid output and EC50 values for OX1R, but not OX2R, was observed. These results suggested that the orexin-A-induced acid stimulation requires OX1R activation and that disulfide bonds in orexin-A may have a key role in the receptor activation. 相似文献
82.
83.
Immature starfish oocytes are surrounded by envelopes consisting of follicular cells. These cells adhere to each other and to the oocyte, immobilizing the latter within the ovary. When isolated oocytes in their follicles are treated with 1-methyladenine (1-MeAde), germinal vesicle breakdown (GVBD) and follicular envelope breakdown (FEBD) occur simultaneously. The 1-MeAde acts on the oocyte surface to produce a maturation-promoting factor (MPF) in the cytoplasm, which brings about GVBD. In the present study, MPF was found to induce FEBD as well as GVBD when injected into immature oocytes with their follicles in Asterina pectinifera. Although GVBD was induced by MPF in the presence of cytochalasin D, this drug prevented MPF-induced FEBD, and each follicular cell remained in situ on the surface of the oocyte. However, desmosomes connecting the processes of the follicle cell with the oocyte surface were disrupted following MPF injection even in the presence of cytochalasin D, and the processes became detached from the oocyte. FEBD occurred in these oocytes when cytochalasin D was removed, resulting in the formation of a small follicular clump by microfilament-mediated contraction of the follicle cells. These results show that FEBD is not brought about by the direct action of 1-MeAde but by the action of MPF. Therefore, in starfish, spawning as well as oocyte maturation is directly triggered by MPF produced under the influence of 1-MeAde. 相似文献
84.
Fully grown oocytes of the starfish Asterina pectinifera, undergo breakdown of their germinal vesicles and subsequent maturation on treatment with 1-methyladenine (1-MeAde). However, oocytes treated with seawater containing 0.010% Triton X-100 lost the capacity to respond to 1-MeAde and their germinal vesicles remained intact. These decapacitated oocytes once again ac-quired the capacity to respond to l-Me Ade when they were incubated in sea water containing the extract of fully grown oocytes treated with Triton X-100, from which the Triton X-100 was removed after extraction by means of Bio-Beads SM-2 (TXE). Recovery of the capacity was also observed after washing such TXE-treated oocytes with sea water. These results suggest that some factor (probably 1-MeAde receptor or its fragment), extracted from the oocyte surface (plasma mem-brane) by nonionic detergent, was reconstituted on the oocyte surface so that the capacity of the oocytes to respond to 1-MeAde was recovered. The factor was heat-stable and resistant to treat-ment with proteolytic enzymes. 相似文献
85.
Takao Suzuki Minoru Moriya Toshihiro Sakamoto Takuya Suga Hiroyuki Kishino Hidekazu Takahashi Makoto Ishikawa Keita Nagai Yumiko Imai Etsuko Sekino Masahiko Ito Hisashi Iwaasa Akane Ishihara Shigeru Tokita Akio Kanatani Nagaaki Sato Takehiro Fukami 《Bioorganic & medicinal chemistry letters》2009,19(11):3072-3077
Optimization of high-throughput screening hit 1a led to the identification of a novel spiro-piperidine class of melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. Compound 3c was identified as a highly potent and selective MCH-1R antagonist, which has an IC50 value of 0.09 nM at hMCH-1R. The synthesis and structure–activity relationships of the novel spiro-piperidine MCH-1R antagonists are described. 相似文献
86.
87.
Minoru Moriya Hiroyuki Kishino Shunji Sakuraba Toshihiro Sakamoto Takuya Suga Hidekazu Takahashi Takao Suzuki Masahiko Ito Junko Ito Ryuichi Moriya Norihiro Takenaga Hisashi Iwaasa Akane Ishihara Akio Kanatani Takehiro Fukami 《Bioorganic & medicinal chemistry letters》2009,19(13):3568-3572
A series of 2-aminobenzimidazole-based MCH1R antagonists was identified by core replacement of the aminoquinoline lead 1. Subsequent modification of the 2- and 5-positions led to improvement in potency and intrinsic clearance. Compound 25 exhibited good plasma and brain exposure, and attenuated MCH induced food intake at 30 mg/kg PO in rats. 相似文献
88.
Hirobumi Takahashi Yuji Haga Takunobu Shibata Katsumasa Nonoshita Toshihiro Sakamoto Minoru Moriya Tomoyuki Ohe Masato Chiba Yuko Mitobe Hidefumi Kitazawa Hisashi Iwaasa Akane Ishihara Yasuyuki Ishii Akio Kanatani Takehiro Fukami 《Bioorganic & medicinal chemistry letters》2009,19(18):5436-5439
A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1′-cyclohexane]-4′-carboxamide derivatives were synthesized and profiled for NPY Y5 binding affinity, brain and CSF penetrability in rats, and susceptibility to human and mouse P-glycoprotein transporters in order to develop a PET ligand. Compound 12b exhibited an acceptable profile for a PET ligand, and [11C]12b was successfully utilized in clinical settings as a Y5 PET ligand. 相似文献
89.
Makoto Ando Nagaaki Sato Tsuyoshi Nagase Keita Nagai Shiho Ishikawa Hirobumi Takahashi Norikazu Ohtake Junko Ito Mioko Hirayama Yuko Mitobe Hisashi Iwaasa Akira Gomori Hiroko Matsushita Kiyoshi Tadano Naoko Fujino Sachiko Tanaka Tomoyuki Ohe Akane Ishihara Akio Kanatani Takehiro Fukami 《Bioorganic & medicinal chemistry》2009,17(16):6106-6122
A series of 2-pyridone-containing imidazoline derivatives was synthesized and evaluated as neuropeptide Y Y5 receptor antagonists. Optimization of the 2-pyridone structure on the 2-position of the imidazoline ring led to identification of 1-(difluoromethyl)-5-[(4S,5S)-4-(4-fluorophenyl)-4-(6-fluoropyridin-3-yl)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]pyridin-2(1H)-one (7m). Compound 7m displayed statistically significant inhibition of food intake in an agonist-induced food intake model in SD rats and no adverse cardiovascular effects in anesthetized dogs. In addition, markedly higher brain penetrability and a lower plasma Occ90 value were observed in P-gp-deficient mdr1a (?/?) mice compared to mdr1a (+/+) mice after oral administration of 7m. 相似文献
90.
Siqi Tian Jun Ohtsuka Shipeng Wang Koji Nagata Masaru Tanokura Akinori Ohta Hiroyuki Horiuchi Ryouichi Fukuda 《Biochemical and biophysical research communications》2014
CTP:phosphoethanolamine cytidylyltransferase (ECT) is a key enzyme in the CDP-ethanolamine branch of the Kennedy pathway, which is the primary pathway of phosphatidylethanolamine (PE) synthesis in mammalian cells. Here, the enzymatic properties of recombinant human ECT (hECT) were characterized. The catalytic reaction of hECT obeyed Michaelis–Menten kinetics with respect to both CTP and phosphoethanolamine. hECT is composed of two tandem cytidylyltransferase (CT) domains as ECTs of other organisms. The histidines, especially the first histidine, in the CTP-binding motif HxGH in the N-terminal CT domain were critical for its catalytic activity in vitro, while those in the C-terminal CT domain were not. Overexpression of the wild-type hECT and hECT mutants containing amino acid substitutions in the HxGH motif in the C-terminal CT domain suppressed the growth defect of the Saccharomyces cerevisiae mutant of ECT1 encoding ECT in the absence of a PE supply via the decarboxylation of phosphatidylserine, but overexpression of hECT mutants of the N-terminal CT domain did not. These results suggest that the N-terminal CT domain of hECT contributes to its catalytic reaction, but C-terminal CT domain does not. 相似文献