全文获取类型
收费全文 | 8755篇 |
免费 | 545篇 |
国内免费 | 7篇 |
专业分类
9307篇 |
出版年
2022年 | 36篇 |
2021年 | 81篇 |
2020年 | 43篇 |
2019年 | 55篇 |
2018年 | 82篇 |
2017年 | 89篇 |
2016年 | 123篇 |
2015年 | 184篇 |
2014年 | 222篇 |
2013年 | 497篇 |
2012年 | 407篇 |
2011年 | 405篇 |
2010年 | 270篇 |
2009年 | 274篇 |
2008年 | 414篇 |
2007年 | 441篇 |
2006年 | 413篇 |
2005年 | 419篇 |
2004年 | 413篇 |
2003年 | 388篇 |
2002年 | 368篇 |
2001年 | 346篇 |
2000年 | 347篇 |
1999年 | 283篇 |
1998年 | 139篇 |
1997年 | 131篇 |
1996年 | 94篇 |
1995年 | 96篇 |
1994年 | 84篇 |
1993年 | 79篇 |
1992年 | 217篇 |
1991年 | 174篇 |
1990年 | 163篇 |
1989年 | 177篇 |
1988年 | 160篇 |
1987年 | 122篇 |
1986年 | 119篇 |
1985年 | 110篇 |
1984年 | 89篇 |
1983年 | 78篇 |
1982年 | 51篇 |
1981年 | 47篇 |
1980年 | 54篇 |
1979年 | 56篇 |
1978年 | 59篇 |
1977年 | 43篇 |
1976年 | 36篇 |
1975年 | 36篇 |
1974年 | 46篇 |
1973年 | 51篇 |
排序方式: 共有9307条查询结果,搜索用时 0 毫秒
971.
972.
Remi Kamakura Myoung Jin Son Dalene de Beer Elizabeth Joubert Yutaka Miura Kazumi Yagasaki 《Cytotechnology》2015,67(4):699-710
Previous studies have demonstrated antidiabetic effects for rooibos (Aspalathus linearis) and aspalathin (ASP), one of its main polyphenols. Rooibos, an endemic plant of South Africa, is well-known for its use as herbal tea. Green (‘unfermented’) rooibos has been shown to contain more ASP than ‘fermented’ rooibos tea, currently the major product. In the present study, we investigated the antidiabetic effect of green rooibos extract (GRE) through studies on glucose uptake in L6 myotubes and on pancreatic β-cell protective ability from reactive oxygen species (ROS) in RIN-5F cells. Its in vivo effect was also examined using obese diabetic KK-Ay mice. GRE increased glucose uptake under insulin absent condition and induced phosphorylation of 5′-adenosine monophosphate-activated protein kinase (AMPK) in L6 myotubes as previously demonstrated for ASP. In addition to AMPK, GRE also promoted phosphorylation of Akt, another promoter of glucose transporter 4 (GLUT4) translocation, in L6 myotubes unlike ASP, suggesting an involvement of GRE component(s) other than ASP in Akt phosphorylation. Promotion of GLUT4 translocation to the plasma membrane by GRE in L6 myotubes was demonstrated by Western blotting analysis. GRE suppressed the advanced glycation end products (AGEs)-induced increase in ROS levels in RIN-5F pancreatic β-cells. Subchronic feeding with GRE suppressed the increase in fasting blood glucose levels in type 2 diabetic model KK-Ay mice. These in vitro and in vivo results strongly suggest that GRE has antidiabetic potential through multiple modes of action. 相似文献
973.
Holger Maier Christine Schütt Ralph Steinkamp Anja Hurt Elida Schneltzer Philipp Gormanns Christoph Lengger Mark Griffiths David Melvin Neha Agrawal Rafael Alcantara Arthur Evans David Gannon Simon Holroyd Christian Kipp Navis Pretheeba Raj David Richardson Sophie LeBlanc Laurent Vasseur Hiroshi Masuya Kimio Kobayashi Tomohiro Suzuki Nobuhiko Tanaka Shigeharu Wakana Alison Walling David Clary Juan Gallegos Helmut Fuchs Martin Hrabě de Angelis Valerie Gailus-Durner 《Mammalian genome》2015,26(9-10):467-481
974.
975.
976.
Aya Nagaoka Hiroyuki Yoshida Sachiko Nakamura Tomohiko Morikawa Keigo Kawabata Masaki Kobayashi Shingo Sakai Yoshito Takahashi Yasunori Okada Shintaro Inoue 《The Journal of biological chemistry》2015,290(52):30910-30923
Regulation of hyaluronan (HA) synthesis and degradation is essential to maintenance of extracellular matrix homeostasis. We recently reported that HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization), also called KIAA1199, plays a key role in HA depolymerization in skin and arthritic synovial fibroblasts. However, regulation of HA metabolism mediated by HYBID and HA synthases (HASs) under stimulation with growth factors remains obscure. Here we report that TGF-β1, basic FGF, EGF, and PDGF-BB commonly enhance total amount of HA in skin fibroblasts through up-regulation of HAS expression, but molecular size of newly produced HA is dependent on HYBID expression levels. Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-β1 were abrogated by blockade of the MAPK and/or Smad signaling and the PI3K-Akt signaling, respectively. In normal human skin, expression of the TGF-β1 receptors correlated positively with HAS2 expression and inversely with HYBID expression. On the other hand, TGF-β1 up-regulated HAS1/2 expression but exerted only a slight suppressive effect on HYBID expression in synovial fibroblasts from the patients with osteoarthritis or rheumatoid arthritis, resulting in the production of lower molecular weight HA compared with normal skin and synovial fibroblasts. These data demonstrate that although TGF-β1, basic FGF, EGF, and PDGF-BB enhance HA production in skin fibroblasts, TGF-β1 most efficiently contributes to production of high molecular weight HA by HAS up-regulation and HYBID down-regulation and suggests that inefficient down-regulation of HYBID by TGF-β1 in arthritic synovial fibroblasts may be linked to accumulation of depolymerized HA in synovial fluids in arthritis patients. 相似文献
977.
Yuka Kobayashi Norikazu Kiguchi Yohji Fukazawa Fumihiro Saika Takehiko Maeda Shiroh Kishioka 《The Journal of biological chemistry》2015,290(20):12603-12613
Peripheral neuroinflammation caused by activated immune cells can provoke neuropathic pain. Herein, we investigate the actions of macrophages and T cells through glucocorticoid-induced tumor neurosis factor receptor ligand (GITRL) and its receptor (GITR) in neuropathic pain. After partial sciatic nerve ligation (PSL) in enhanced green fluorescent protein (eGFP) chimeric mice generated by the transplantation of eGFP+ bone marrow cells, eGFP+ macrophages, and T cells markedly migrated to the injured site after PSL. Administration of agents to deplete macrophages (liposome-clodronate and Clophosome-ATM) or T cells (anti-CD4 antibody and FTY720) could suppress PSL-induced thermal hyperalgesia and tactile allodynia. The expression levels of co-stimulatory molecules GITRL and GITR were increased on infiltrating macrophages and T cells, respectively. The perineural injection of a GITRL neutralizing antibody that could inhibit the function of the GITRL-GITR pathway attenuated PSL-induced neuropathic pain. Additionally, the induction of inflammatory cytokines and the accumulation of GITR+ T cells in the injured SCN were abrogated after macrophage depletion by Clophosome-ATM. In conclusion, GITRL expressed on macrophages drives cytokine release and T cell activation, resulting in neuropathic pain via GITR-dependent actions. The GITRL-GITR pathway might represent a novel target for the treatment of neuropathic pain. 相似文献
978.
979.
Yuichi Wakana Richika Kotake Nanako Oyama Motohide Murate Toshihide Kobayashi Kohei Arasaki Hiroki Inoue Mitsuo Tagaya 《Molecular biology of the cell》2015,26(25):4686-4699
Vesicle-associated membrane protein–associated protein (VAP) is an endoplasmic reticulum (ER)-resident integral membrane protein that controls a nonvesicular mode of ceramide and cholesterol transfer from the ER to the Golgi complex by interacting with ceramide transfer protein and oxysterol-binding protein (OSBP), respectively. We report that VAP and its interacting proteins are required for the processing and secretion of pancreatic adenocarcinoma up-regulated factor, whose transport from the trans-Golgi network (TGN) to the cell surface is mediated by transport carriers called “carriers of the trans-Golgi network to the cell surface” (CARTS). In VAP-depleted cells, diacylglycerol level at the TGN was decreased and CARTS formation was impaired. We found that VAP forms a complex with not only OSBP but also Sac1 phosphoinositide phosphatase at specialized ER subdomains that are closely apposed to the trans-Golgi/TGN, most likely reflecting membrane contact sites. Immobilization of ER–Golgi contacts dramatically reduced CARTS production, indicating that association–dissociation dynamics of the two membranes are important. On the basis of these findings, we propose that the ER–Golgi contacts play a pivotal role in lipid metabolism to control the biogenesis of transport carriers from the TGN. 相似文献
980.