全文获取类型
收费全文 | 568篇 |
免费 | 47篇 |
国内免费 | 1篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 10篇 |
2020年 | 8篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 12篇 |
2014年 | 17篇 |
2013年 | 34篇 |
2012年 | 34篇 |
2011年 | 40篇 |
2010年 | 19篇 |
2009年 | 15篇 |
2008年 | 24篇 |
2007年 | 25篇 |
2006年 | 28篇 |
2005年 | 26篇 |
2004年 | 32篇 |
2003年 | 25篇 |
2002年 | 33篇 |
2001年 | 20篇 |
2000年 | 24篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 8篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 13篇 |
1993年 | 3篇 |
1992年 | 14篇 |
1991年 | 6篇 |
1990年 | 13篇 |
1989年 | 9篇 |
1988年 | 6篇 |
1987年 | 7篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 9篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有616条查询结果,搜索用时 250 毫秒
21.
Adrenal pheochromocytoma PC12h cells respond to pituitary adenylate cyclase activating polypeptide 总被引:2,自引:0,他引:2
T Watanabe T Ohtaki C Kitada M Tsuda M Fujino 《Biochemical and biophysical research communications》1990,173(1):252-258
An adrenal pheochromocytoma cell line, PC12h, was found to respond to a novel hypothalamic neuropeptide, Pituitary Adenylate Cyclase Activating Polypeptide (PACAP). The cells elevated both intracellular and extracellular cAMP levels on stimulation by PACAP, whereas they showed little response to VIP which is structurally related to PACAP. Using [125I]PACAP27 (a shorter form of the peptide) and [125I]VIP, we found large amounts of specific binding sites for PACAP but few binding sites for VIP in PC12h cells. These results indicate that PC12h cells respond to PACAP via a specific PACAP receptor. 相似文献
22.
23.
M Kitada K Igarashi S Hirose H Kitagawa 《Biochemical and biophysical research communications》1979,87(2):388-394
Both NADPH- and ascorbic acid-dependent lipid peroxidations were inhibited by spermine, the degree of inhibition being greater with the former peroxidation. The effective concentration of spermine required for inhibition was higher when larger amounts of microsomes were used. However, the activities of NADPH-cytochrome c reductase and NADPH-peroxidase were not influenced by spermine. These results suggest that spermine inhibits lipid peroxidation by binding to phospholipids in the microsomes. 相似文献
24.
Hemma Brandstaetter Chieko Kishi-Itakura David A Tumbarello Dietmar J Manstein Folma Buss 《Autophagy》2014,10(12):2310-2323
MYO1C, a single-headed class I myosin, associates with cholesterol-enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional MYO1C disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol-enriched membranes in the perinuclear recycling compartment, and leads to enlargement of endolysosomal membranes. Several feeder pathways, including classical endocytosis but also the autophagy pathway, maintain the health of the cell by selective degradation of cargo through fusion with the lysosome. Here we show that loss of functional MYO1C leads to an increase in total cellular cholesterol and its disrupted subcellular distribution. We observe an accumulation of autophagic structures caused by a block in fusion with the lysosome and a defect in autophagic cargo degradation. Interestingly, the loss of MYO1C has no effect on degradation of endocytic cargo such as EGFR, illustrating that although the endolysosomal compartment is enlarged in size, it is functional, contains active hydrolases, and the correct pH. Our results highlight the importance of correct lipid composition in autophagosomes and lysosomes to enable them to fuse. Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway. 相似文献
25.
Nobuo Kitada Ryohei Saito Rika Obata Satoshi Iwano Kazuma Karube Atsushi Miyawaki Takashi Hirano Shojiro A. Maki 《Chirality》2020,32(7):922-931
Interestingly, only the D-form of firefly luciferin produces light by luciferin–luciferase (L–L) reaction. Certain firefly luciferin analogues with modified structures maintain bioluminescence (BL) activity; however, all L-form luciferin analogues show no BL activity. To this date, our group has developed luciferin analogues with moderate BL activity that produce light of various wavelengths. For in vivo bioluminescence imaging, one of the important factors for detection sensitivity is tissue permeability of the number of photons emitted by L–L reaction, and the wavelengths of light in the near-infrared (NIR) range (700–900 nm) are most appropriate for the purpose. Some NIR luciferin analogues by us had performance for in vivo experiments to make it possible to detect photons from deep target tissues in mice with high sensitivity, whereas only a few of them can produce NIR light by the L–L reactions with wild-type luciferase and/or mutant luciferase. Based on the structure–activity relationships, we designed and synthesized here a luciferin analogue with the 5-allyl-6-dimethylamino-2-naphthylethenyl moiety. This analogue exhibited NIR BL emissions with wild-type luciferase (λmax = 705 nm) and mutant luciferase AlaLuc (λmax = 655 nm). 相似文献
26.
27.
28.
Keisuke Ueda Chieko Kimura-Sakiyama Tomoki Aihara Masao Miki Toshiaki Arata 《Biophysical journal》2013
To identify the interaction sites of Tm, we measured the rotational motion of a spin-label covalently bound to the side chain of a cysteine that was genetically incorporated into rabbit skeletal muscle tropomyosin (Tm) at positions 13, 36, 146, 160, 174, 190, 209, 230, 271, or 279. Most of the Tm residues were immobilized on actin filaments with myosin-S1 bound to them. The residues in the mid-portion of Tm, namely, 146, 174, 190, 209, and 230, were mobilized when the troponin (Tn) complex bound to the actin-Tm-S1 filaments. The addition of Ca2+ ions partially reversed the Tn-induced mobilization. In contrast, residues at the joint region of Tm, 13, 36, 271, and 279 were unchanged or oppositely changed. All of these changes were detected using a maleimide spin label and less obviously using a methanesulfonate label. These results indicated that Tm was fixed on thin filaments with myosin bound to them, although a small change in the flexibility of the side chains of Tm residues, presumably interfaced with Tn, actin and myosin, was induced by the binding of Tn and Ca2+. These findings suggest that even in the myosin-bound (open) state, Ca2+ may regulate actomyosin contractile properties via Tm. 相似文献
29.
30.
Ling Xu Megumi Kanasaki Jianhua He Munehiro Kitada Kenji Nagao Hiroko Jinzu Yasushi Noguchi Hiroshi Maegawa Keizo Kanasaki Daisuke Koya 《生物化学与生物物理学报:疾病的分子基础》2013,1832(10):1605-1612
Ketogenic amino acid (KAA) replacement diet has been shown to cure hepatic steatosis, a serious liver disease associated with diverse metabolic defects. In this study, we investigated the effects of KAA replacement diet on nutrition sensing signaling pathway and analyzed whether induction of hepatic autophagy was involved. Mice are fed with high fat diet (HFD) or KAA replacement in high-fat diet (30% fat in food; HFD)-fed (HFDKAAR) and sacrificed at 8, 12, 16 weeks after initiation of experimental food. Hepatic autophagy was analyzed in protein expression of several autophagy-associated molecules and in light chain-3 green fluorescent protein (LC-3 GFP) transgenic mice. HFDKAAR showed increased AMP-activated protein kinase (AMPK) phosphorylation and enhanced liver kinase B1 (LKB1) expression compared to control HFD-fed mice. The KAA-HFD-induced activation of AMPK was associated with an increased protein expression of sirtuin 1 (Sirt1), decreased forkhead box protein O3a (Foxo3a) level, and suppression of mammalian target of rapamycin (mTOR) phosphorylation compared with the HFD-fed mice. The intervention study revealed that a KAA-replacement diet also ameliorated all the established metabolic and autophagy defects in the HFD-fed mice, suggesting that a KAA-replacement diet can be used therapeutically in established diseases. These results indicate that KAA replacement in food could be a novel strategy to combat hepatic steatosis and metabolic abnormalities likely involvement of an induction of autophagy. 相似文献