全文获取类型
收费全文 | 195篇 |
免费 | 13篇 |
专业分类
208篇 |
出版年
2021年 | 2篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 3篇 |
2013年 | 7篇 |
2012年 | 7篇 |
2011年 | 3篇 |
2010年 | 5篇 |
2009年 | 7篇 |
2008年 | 9篇 |
2007年 | 8篇 |
2006年 | 9篇 |
2005年 | 4篇 |
2004年 | 7篇 |
2003年 | 5篇 |
2002年 | 6篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 10篇 |
1990年 | 8篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 7篇 |
1969年 | 1篇 |
1968年 | 3篇 |
1967年 | 1篇 |
1965年 | 2篇 |
1959年 | 1篇 |
排序方式: 共有208条查询结果,搜索用时 15 毫秒
21.
Urano E Kariya Y Futahashi Y Ichikawa R Hamatake M Fukazawa H Morikawa Y Yoshida T Koyanagi Y Yamamoto N Komano J 《FEBS letters》2008,582(29):4053-4058
We conducted a phenotypic cDNA screening using a T cell line-based assay to identify human genes that render cells resistant to human immunodeficiency virus type 1 (HIV-1). We isolated potential HIV-1 resistance genes, including the carboxy terminal domain (CTD) of bromodomain-containing protein 4 (Brd4). Expression of GFP-Brd4-CTD was tolerated in MT-4 and Jurkat cells in which HIV-1 replication was markedly inhibited. We provide direct experimental data demonstrating that Brd4-CTD serves as a specific inhibitor of HIV-1 replication in T cells. Our method is a powerful tool for the identification of host factors that regulate HIV-1 replication in T cells. 相似文献
22.
Lazareno S Birdsall B Fukazawa T Gharagozloo P Hashimoto T Kuwano H Popham A Sugimoto M Birdsall NJ 《Life sciences》1999,64(6-7):519-526
We previously demonstrated that brucine and some analogues allosterically enhance the affinity of ACh at muscarinic receptor subtypes M1, M3 or M4. Here we describe allosteric effects at human M1-M4 receptors of four stereoisomers of a pentacyclic structure containing features of the ring structure of brucine. All compounds inhibited 3H-NMS dissociation almost completely at all subtypes with slopes of 1, with similar affinity values at the 3H-NMS-occupied receptor to those estimated from equilibrium assays, consistent with the ternary complex allosteric model. Compound 1a showed positive cooperativity with H-NMS and small negative or neutral cooperativity with ACh at all subtypes. Its stereoisomer, 1b, showed strong negative cooperativity with both 3H-NMS and ACh across the subtypes. Compound 2a was positive with 3H-NMS at M2 and M4 receptors, neutral at M3 and negative at M1 receptors; it was negatively cooperative with ACh at all subtypes. Its stereoisomer, 2b, was neutral with 3H-NMS at M1 receptors and positive at the other subtypes; 2b was negatively cooperative with ACh at M1, M3 and M4 receptors but showed 3-fold positive cooperativity with ACh at M2 receptors. This latter result was confirmed with further 3H-NMS and 3H-ACh radioligand binding assays and with functional assays of ACh-stimulated 35S-GTPgammaS binding. These results provide the first well characterised instance of a positive enhancer of ACh at M2 receptors, and illustrate the difficulty of predicting such an effect. 相似文献
23.
24.
25.
26.
27.
Calcium alginate beads covalently linked with alpha-cyclodextrin (alpha-CD-alginate beads) were prepared and examined for their ability to serve as a supporting matrix for bacterial degradation of nonylphenol, an endocrine disruptor. Column chromatographic experiment using alpha-CD-alginate beads with diameter of 657+/-82 microm and with degree of CD substitution of 0.16 showed a strong affinity for nonylphenol adsorption. Although addition of alpha-CD (2.7-27 mM) to the culture broth of Sphingomonas cloacae retarded nonylphenol degradation, the immobilized bacteria on the CD-alginate beads were effective for the degradation. Batch degradation tests using the immobilized bacteria on alpha-CD-alginate-beads showed 46% nonylphenol recovery after 10-day incubation at 25+/-2 degrees C, and the recovery reached to about 17% when wide and shallow incubation tubes were used to facilitate uptake of the viscous liquid of nonylphenol on the surface of the medium. Scanning electron microscopic photographs revealed that multiplicated bacteria was present both on the surface and inside the beads and the matrix of CD-alginate was stable and suitable during 10-day incubation. 相似文献
28.
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
29.
Gene delivery to embryonic stem cells 总被引:1,自引:0,他引:1
Kobayashi N Rivas-Carrillo JD Soto-Gutierrez A Fukazawa T Chen Y Navarro-Alvarez N Tanaka N 《Birth defects research. Part C, Embryo today : reviews》2005,75(1):10-18
Since the establishment of embryonic stem (ES) cells and the identification of tissue-specific stem cells, researchers have made great strides in the analysis of the natural biology of such stem cells for the development of therapeutic applications. Specifically, ES cells are capable of differentiating into all of the cell types that constitute the whole body. Thus, ES cell research promises new type of treatments and possible cures for a variety of debilitating diseases and injuries. The potential medical benefits obtained from stem cell technology are compelling and stem cell research sees a bright future. Control of the growth and differentiation of stem cells is a critical tool in the fields of regenerative medicine, tissue engineering, drug discovery, and toxicity testing. Toward such a goal, we present here an overview of gene delivery in ES cells, covering the following topics: significance of gene delivery in ES cells, stable versus transient gene delivery, cytotoxicity, suspension versus adherent cells, expertise, time, cost, viral vectors for gene transduction (lentiviruses, adenoviruses, and adeno-associated viruses, chemical methods for gene delivery, and mechanical or physical gene delivery methods (electroporation, nucleofection, microinjection, and nuclear transfer). 相似文献
30.
Saito K Watanabe Y Shirakawa M Matsushita Y Imai T Koike T Sano Y Funada R Fukazawa K Fukushima K 《The Plant journal : for cell and molecular biology》2012,69(3):542-552
Lignin, one of the main structural polymer of plant cell walls, varies in amount and monomeric composition among tissue and cell types, as well as among plant species. However, few analytical methods are available that can conveniently and accurately determine the morphological distribution of lignin units at the cellular level. In this report, we used time-of-flight secondary ion mass spectrometry (TOF-SIMS) to directly map guaiacyl (G) and syringyl (S) lignin units in several successive growth rings of the maple xylem. TOF-SIMS imaging and a semiquantitative approach revealed clear difference in the annual distribution of lignins between the fiber and vessel. While the vessel walls were constantly G-rich with varied S/G ratios through a growth ring, the fibers showed fairly regular annual distribution of lignins in which the earlywood was S-rich with an almost constant S/G ratio and the latewood was G-rich resulting from a decrease of the S unit. The reliability of TOF-SIMS results was demonstrated by its high correlation with the results of thioacidolysis on radial distribution of the S/G ratio in several contiguous tree rings and also in the latewood and earlywood of each ring. These results indicate that TOF-SIMS allows direct visualization of lignin composition in plant tissues. 相似文献