全文获取类型
收费全文 | 537篇 |
免费 | 51篇 |
国内免费 | 5篇 |
出版年
2023年 | 2篇 |
2021年 | 13篇 |
2020年 | 1篇 |
2019年 | 5篇 |
2018年 | 9篇 |
2017年 | 5篇 |
2016年 | 13篇 |
2015年 | 33篇 |
2014年 | 27篇 |
2013年 | 33篇 |
2012年 | 46篇 |
2011年 | 38篇 |
2010年 | 25篇 |
2009年 | 14篇 |
2008年 | 24篇 |
2007年 | 27篇 |
2006年 | 23篇 |
2005年 | 23篇 |
2004年 | 34篇 |
2003年 | 21篇 |
2002年 | 27篇 |
2001年 | 11篇 |
2000年 | 15篇 |
1999年 | 13篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 1篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 13篇 |
1991年 | 4篇 |
1990年 | 13篇 |
1989年 | 7篇 |
1988年 | 3篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有593条查询结果,搜索用时 968 毫秒
101.
Hiromitsu Negoro Marcia Urban-Maldonado Louis S. Liou David C. Spray Mia M. Thi Sylvia O. Suadicani 《PloS one》2014,9(8)
Urothelial cells respond to bladder distension with ATP release, and ATP signaling within the bladder and from the bladder to the CNS is essential for proper bladder function. In other cell types, pannexin 1 (Panx1) channels provide a pathway for mechanically-induced ATP efflux and for ATP-induced ATP release through interaction with P2X7 receptors (P2X7Rs). We report that Panx1 and P2X7R are functionally expressed in the bladder mucosa and in immortalized human urothelial cells (TRT-HU1), and participate in urothelial ATP release and signaling. ATP release from isolated rat bladders induced by distention was reduced by the Panx1 channel blocker mefloquine (MFQ) and was blunted in mice lacking Panx1 or P2X7R expression. Hypoosmotic shock induced YoPro dye uptake was inhibited by MFQ and the P2X7R blocker A438079 in TRT-HU1 cells, and was also blunted in primary urothelial cells derived from mice lacking Panx1 or P2X7R expression. Rinsing-induced mechanical stimulation of TRT-HU1 cells triggered ATP release, which was reduced by MFQ and potentiated in low divalent cation solution (LDPBS), a condition known to enhance P2X7R activation. ATP signaling evaluated as intercellular Ca2+ wave radius was significantly larger in LDPBS, reduced by MFQ and by apyrase (ATP scavenger). These findings indicate that Panx1 participates in urothelial mechanotransduction and signaling by providing a direct pathway for mechanically-induced ATP release and by functionally interacting with P2X7Rs. 相似文献
102.
Resistance nodulation division (RND) efflux pumps, such as the SmeIJK pump of Stenotrophomonas maltophilia, are known to contribute to the multidrug resistance in Gram-negative bacteria. However, some RND pumps are constitutively expressed even though no antimicrobial stresses occur, implying that there should be some physical implications for these RND pumps. In this study, the role of SmeIJK in antimicrobials resistance, envelope integrity, and σE-mediated envelope stress response (ESR) of S. maltophilia was assessed. SmeIJK was involved in the intrinsic resistance of S. maltophilia KJ to aminoglycosides and leucomycin. Compared with the wild-type KJ, the smeIJK deletion mutant exhibited growth retardation in the MH medium, an increased sensitivity to membrane-damaging agents (MDAs), as well as activation of an σE-mediated ESR. Moreover, the expression of smeIJK was further induced by sub-lethal concentrations of MDAs or surfactants in an σE-dependent manner. These data collectively suggested an alternative physiological role of smeIJK in cell envelope integrity maintenance and σE-mediated ESR beyond the efflux of antibiotics. Because of the necessity of the physiological role of SmeIJK in protecting S. maltophilia from the envelope stress, smeIJK is constitutively expressed, which, in turn, contributes the intrinsic resistance to aminoglycoside and leucomycin. This is the first demonstration of the linkage among RND-type efflux pump, cell envelope integrity, and σE-mediated ESR in S. maltophilia. 相似文献
103.
用蔗糖密度梯度离心提纯的6种昆虫病毒包涵体(BsNPV1,BsNPV2,BtNPV,EpNPV,PrGV,PxGV)经DAS碱解,粗提纯的包涵体蛋白经Sepharose-6B柱层析和Caaalco-prep-disc法进一步纯化后,在SDS-PAGE中显示为一条分子量约28,000d的带。用常规双向免疫扩散法检查各种包涵体蛋白之间的差异,结果表明血清学BsNPV与BtNPV,PrGV与PxGV之间都是不可分辩的。6种包涵体蛋白的双向高压指纹图谱表明,它们的指纹图谱都不同程度地存在着一些相同或十分相似的肽点。就每种病毒的指纹图谱又都是独特的,NPV间相似性低于GV间相似性。我们认为NPV和GV的包涵体蛋白在结构上存在着一些相同的或相似的保守区域,但不同种之间在整个一级结构上是有差异的。利用包涵体蛋白的指纹图谱鉴定杆状病毒是个灵敏可行的方法。 相似文献
104.
Chih-Yang Huang Tsai-Ching Hsu Wei-Wen Kuo Yi-Fan Liou Shin-Da Lee Da-Tong Ju Chia-Hua Kuo Bor-Show Tzang 《PloS one》2015,10(5)
The roots of the perennial herb Gentiana macrophylla Pall. (GM) are known as Qinjiao, which has been used for centuries to treat systemic lupus erythematosus (SLE). However, little is known about the effects of GM on cholesterol-aggravated cardiac abnormalities in SLE, and the mechanisms thereof. This study investigates whether GM exhibits anti-apoptotic effects, focusing on the left ventricle (LV) of NZB/W F1 mice fed with high-cholesterol diet. The morphology and apoptotic status of ventricular tissues were determined by microscopy and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Levels of apoptotic biomarkers were determined by immunoblotting. The results thus obtained revealed that GM significantly reduced the cholesterol-aggravated apoptosis of LV in NZB/W F1 mice by suppressing both intrinsic and extrinsic apoptotic pathways. Additionally, GM significantly increased the cardiac insulin-like growth factors (IGF)-1 survival signaling and anti-apoptotic proteins in LV tissues. Accordingly, GM is considered to be beneficial in alleviating cholesterol-aggravated cardiac damage in SLE, and therefore constitute an alternative treatment for SLE patients with cardiac abnormalities. 相似文献
105.
Tsuyoshi Nishioku Koichi Hashimoto Keizo Yamashita Shyh-Yuh Liou Yoshifumi Kagamiishi Hitoshi Maegawa Nobuo Katsube Christoph Peters Kurt von Figura Paul Saftig Nobuhiko Katunuma Kenji Yamamoto Hiroshi Nakanishi 《The Journal of biological chemistry》2002,277(7):4816-4822
We have attempted to elucidate an involvement of cathepsin E (CE) in major histocompatibility complex class II-mediated antigen presentation by microglia. In primary cultured murine microglia, CE was localized mainly in early endosomes and its expression level was markedly increased upon stimulation with interferon-gamma. Pepstatin A, a specific inhibitor of aspartic proteases, significantly inhibited interleukin-2 production from an OVA-(266-281)-specific T helper cell hybridomas upon stimulation with native OVA presented by interferon-gamma-treated microglia. However, pepstatin A failed to inhibit the presentation of OVA-(266-281) peptide. The possible involvement of CE in the processing of native OVA into antigenic peptide was further substantiated by that digested fragments of native OVA by CE could be recognized by OVA-specific Th cells. Cathepsin D also degraded native OVA into antigenic peptide, whereas microglia prepared from cathepsin D-deficient mice retained an ability for antigen presentation. On the other hand, the requirement for cysteine proteases such as cathepsins S and B in the processing of invariant chain (Ii) was confirmed by immunoblot analyses in the presence of their specific inhibitors. In conclusion, CE is required for the generation of an antigenic epitope from OVA but not for the processing of Ii in microglia. 相似文献
106.
107.
G I Liou L Geng M R al-Ubaidi S Matragoon G Hanten W Baehr P A Overbeek 《The Journal of biological chemistry》1990,265(15):8373-8376
Interphotoreceptor retinoid-binding protein (IRBP) is an extracellular protein that has been suggested to participate in the visual process as a carrier for visual retinoids. A chimeric gene composed of the human IRBP promoter fused to the bacterial reporter gene chloramphenicol acetyltransferase (CAT) was used to generate transgenic mice. Analysis of six transgenic families revealed that the CAT gene, concomitant with the endogenous IRBP gene, was expressed primarily in the retina and, to a lesser extent, in the pineal gland. These results establish that a 1.3-kilobase fragment from the 5' end of the human IRBP gene is sufficient to direct transgene expression to a visual subdivision of the central nervous system. 相似文献
108.
Ruey-Shyan Liou Michael S. C. Fung Ulrich Zühlke Fred Gudat Sam McKinney Wayne Gordon Walter Bee Luigi Botta Daniel Gygax Tse-Wen Chang Nancy T. Chang Dietmar G. Braun MD 《Biotherapy》1992,5(4):291-299
In preparing for testing a pharmaceutical grade preparation of chimeric (mouse/human) antibody CGP 47 439 in HIV-1 infected individuals, it was administered toMacaca fascicularis (cynomolgus) monkeys to study tolerability, immunogenicity and pharmacokinetics. Four groups of monkeys, three males and three females per group, received respectively four infusions of 0, 1.43, 4.3, and 14.3 mg of CGP 47 4391 kg body weight at one-week intervals. The chimeric antibody induced no fever, was tolerated well throughout the 50-day observation period, elicited no tissue damage and no anti-antibody response. The pharmacokinetic profile was similar at all dose levels with a mean T1/2 of 14.2 h (range 11.8–19.3 h) and a mean T1/2 of 172.6h (range 137.2–220.5h). Following four successive antibody infusions serum concentrations of CGP 47 439 increased without reaching a steady state, and its measured concentrations were comparable to the simulated values. Collectively the study has provided safety and pharmacokinetic data that would allow human studies with this antibody in AIDS patients. 相似文献
109.
110.
The implementation of the consensus on the management of Helicobacter pylori and barriers to consensus
下载免费PDF全文
![点击此处可从《Helicobacter》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hsiu‐Chi Cheng Jyh‐Ming Liou Jiing‐Chyuan Luo Cheng‐Tang Chiu Ming‐Shiang Wu Yi‐Chia Lee Chun‐Ying Wu Deng‐Chyang Wu Ping‐I Hsu Chun‐Chao Chang Wei‐Lun Chang Jaw‐Town Lin Bor‐Shyang Sheu 《Helicobacter》2018,23(5)