全文获取类型
收费全文 | 156篇 |
免费 | 11篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 6篇 |
2015年 | 10篇 |
2014年 | 2篇 |
2013年 | 18篇 |
2012年 | 9篇 |
2011年 | 11篇 |
2010年 | 7篇 |
2009年 | 3篇 |
2008年 | 7篇 |
2007年 | 8篇 |
2006年 | 9篇 |
2005年 | 6篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 11篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有167条查询结果,搜索用时 156 毫秒
1.
2.
Shoujun Chen Lijun Sun Keizo Koya Noriaki Tatsuta Zhiqiang Xia Timothy Korbut Zhenjian Du Jim Wu Guiqing Liang Jun Jiang Mitsunori Ono Dan Zhou Andrew Sonderfan 《Bioorganic & medicinal chemistry letters》2013,23(18):5070-5076
A series of N′1,N′3-dialkyl-N′1,N′3-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure–activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol. 相似文献
3.
Kazuya Hayashi Danji Fukushima Koya Mogi 《Bioscience, biotechnology, and biochemistry》2013,77(8):988-994
The molecular conformation of the alkaline proteinase of Aspergillus sojae in aqueous solution was investigated by the optical rotatory dispersion, Cotton effects, infra-red absorption spectra (amide I and V bands), ultraviolet difference spectra, etc. It is concluded that; (1) there are about 10 to 15% of the α-helix and a small amount of the β-structure in the enzyme molecule, but most parts of the peptide chain are present as the disordered structure; (2) the enzyme molecule is compactly folded even in the disordered parts; and (3) the two tryptophan residues involved in the peptide chain are burried in the interior of the molecule. 相似文献
4.
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
5.
Morita Y Araki H Sugimoto T Takeuchi K Yamane T Maeda T Yamamoto Y Nishi K Asano M Shirahama-Noda K Nishimura M Uzu T Hara-Nishimura I Koya D Kashiwagi A Ohkubo I 《FEBS letters》2007,581(7):1417-1424
Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells. 相似文献
6.
7.
Shogo Tamura Masato Mukaide Yumi Katsuragi Wataru Fujii Koya Odaira Nobuaki Suzuki Nagaharu Tsukiji Shuichi Okamoto Atsuo Suzuki Takeshi Kanematsu Akira Katsumi Akira Takagi Katsuhide Ikeda Jun Ueyama Masaaki Hirayama Katsue Suzuki-Inoue Tadashi Matsushita Tetsuhito Kojima Fumihiko Hayakawa 《The Journal of biological chemistry》2022,298(5)
Bone marrow development and endochondral bone formation occur simultaneously. During endochondral ossification, periosteal vasculatures and stromal progenitors invade the primary avascular cartilaginous anlage, which induces primitive marrow development. We previously determined that bone marrow podoplanin (PDPN)-expressing stromal cells exist in the perivascular microenvironment and promote megakaryopoiesis and erythropoiesis. In this study, we aimed to examine the involvement of PDPN-expressing stromal cells in postnatal bone marrow generation. Using histological analysis, we observed that periosteum-derived PDPN-expressing stromal cells infiltrated the cartilaginous anlage of the postnatal epiphysis and populated on the primitive vasculature of secondary ossification center. Furthermore, immunophenotyping and cellular characteristic analyses indicated that the PDPN-expressing stromal cells constituted a subpopulation of the skeletal stem cell lineage. In vitro xenovascular model cocultured with human umbilical vein endothelial cells and PDPN-expressing skeletal stem cell progenies showed that PDPN-expressing stromal cells maintained vascular integrity via the release of angiogenic factors and vascular basement membrane-related extracellular matrices. We show that in this process, Notch signal activation committed the PDPN-expressing stromal cells into a dominant state with basement membrane-related extracellular matrices, especially type IV collagens. Our findings suggest that the PDPN-expressing stromal cells regulate the integrity of the primitive vasculatures in the epiphyseal nascent marrow. To the best of our knowledge, this is the first study to comprehensively examine how PDPN-expressing stromal cells contribute to marrow development and homeostasis. 相似文献
8.
The placozoan Trichoplax adhaerence is one of the most primitive multi-cellular organisms, and moves about accompanying perpetual changes in its shape. Changes in position, locomotion velocity and the outer shape of the organism were monitored quantitatively with use of a computer image analysis, and their dynamic patterns in free locomotion and upon feeding were analyzed in terms of non-linear dynamics. The organism changed its behavioral patterns discontinuously in response to various concentrations of yeast extracts (food). (1) At low concentrations, the organism moved fast with perpetual random changes in shape. Both locomotion velocity and shape changes exhibited 1/f fluctuations. (2) At high concentrations, the shape of the organism as well as the locomotion exhibited oscillations with periods of about 8 min. These limit cycle oscillations bifurcated into the period 2 at the highest concentration tested. The organism flattened more strongly and the locomotion was more reduced on the whole at higher concentrations. (3) At the intermediate concentrations, two patterns as monitored above appeared: one pattern continued for a while and switched to the other abruptly. (4) The average square displacement of the organism increased linearly with time in all cases, indicating that the locomotion is a Brownian movement. In this way, the feeding behaviors by the placozoan are organized as successive co-operative transitions among non-linear dynamic states. 相似文献
9.
Shigematsu S Ishida S Hara M Takahashi N Yoshimatsu H Sakata T Korthuis RJ 《Free radical biology & medicine》2003,34(7):810-817
Moderate consumption of red wine has been shown to exert cardioprotection against ischemia/reperfusion. Because oxidant-dependent leukocyte infiltration plays a critical role in ischemia/reperfusion-induced tissue injury, we hypothesized that resveratrol, a red wine constituent polyphenol would attenuate postischemic leukocyte recruitment and subsequent endothelial dysfunction. Intravital microscopic approaches were used to quantify leukocyte/endothelial cell interactions and venular protein leakage in rat mesenteries exposed to either 20 min ischemia and 60 min reperfusion (I/R), oxidants generated by the reaction of hypoxanthine and xanthine oxidase (HX/XO), platelet-activating factor (PAF), or leukotriene B4 (LTB4). I/R or HX/HX produced marked increases in the number of adherent (LA) and emigrated (LE) leukocytes, which were associated with significant increases in venular albumin leakage (VAL). Intravenous administration of resveratrol or superoxide dismutase (SOD) attenuated these increases in LA, LE, and VAL. Superfusion of the mesentery with PAF or LTB4 also markedly increased LA, LE, and VAL. While resveratrol attenuated the proinflammatory effects of PAF, LTB4-induced changes were not affected by resveratrol. Resveratrol prevents leukocyte recruitment and endothelial barrier disruption induced by a number of superoxide-dependent proinflammatory stimuli, including I/R, HX/XO, or PAF. These salutary effects appear to be related to the antioxidant properties of resveratrol and contribute to the cardioprotective actions associated with consumption of red wine. 相似文献
10.
Development of human T-cell leukemia virus type 1-transformed tumors in rats following suppression of T-cell immunity by CD80 and CD86 blockade 下载免费PDF全文
Hanabuchi S Ohashi T Koya Y Kato H Takemura F Hirokawa K Yoshiki T Yagita H Okumura K Kannagi M 《Journal of virology》2000,74(1):428-435
Host immunity influences clinical manifestations of human T-cell leukemia virus type 1 (HTLV-1) infection. In this study, we demonstrated that HTLV-1-transformed tumors could develop in immunocompetent rats by blocking a costimulatory signal for T-cell immune responses. Four-week-old WKA/HKm rats were treated with monoclonal antibodies (MAbs) to CD80 and CD86 and subcutaneously inoculated with syngeneic HTLV-1-infected TARS-1 cells. During MAb treatment for 14 days, TARS-1 inoculation resulted in the development of solid tumors at the site of inoculation, which metastasized to the lungs. In contrast, rats not treated with MAbs promptly rejected tumor cells. Splenic T cells from MAb-treated rats indicated impairment of proliferative and cytotoxic T-lymphocyte responses against TARS-1 in vitro compared to untreated rats. However, tumors grown in MAb-treated rats regressed following withdrawal of MAb therapy. Recovery of TARS-1-specific T-cell immune responses was associated with tumor regression in these rats. Our results suggest that HTLV-1-specific cell-mediated immunity plays a critical role in immunosurveillance against HTLV-1-transformed tumor development in vivo. 相似文献