全文获取类型
收费全文 | 1009篇 |
免费 | 106篇 |
国内免费 | 1篇 |
出版年
2022年 | 9篇 |
2021年 | 20篇 |
2020年 | 10篇 |
2019年 | 6篇 |
2018年 | 14篇 |
2017年 | 9篇 |
2016年 | 19篇 |
2015年 | 46篇 |
2014年 | 36篇 |
2013年 | 46篇 |
2012年 | 57篇 |
2011年 | 52篇 |
2010年 | 40篇 |
2009年 | 28篇 |
2008年 | 51篇 |
2007年 | 48篇 |
2006年 | 43篇 |
2005年 | 26篇 |
2004年 | 35篇 |
2003年 | 32篇 |
2002年 | 40篇 |
2001年 | 32篇 |
2000年 | 43篇 |
1999年 | 26篇 |
1998年 | 13篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 10篇 |
1992年 | 23篇 |
1991年 | 14篇 |
1990年 | 16篇 |
1989年 | 23篇 |
1988年 | 18篇 |
1987年 | 14篇 |
1986年 | 21篇 |
1985年 | 16篇 |
1984年 | 6篇 |
1983年 | 11篇 |
1981年 | 12篇 |
1980年 | 10篇 |
1979年 | 12篇 |
1978年 | 10篇 |
1977年 | 7篇 |
1976年 | 13篇 |
1975年 | 10篇 |
1974年 | 13篇 |
1973年 | 15篇 |
1972年 | 6篇 |
1971年 | 6篇 |
1968年 | 8篇 |
排序方式: 共有1116条查询结果,搜索用时 312 毫秒
951.
Recent advances in optical imaging have dramatically expanded the capabilities of the light microscope and its usefulness in microbiology research. Some of these advances include improved fluorescent probes, better cameras, new techniques such as confocal and deconvolution microscopy, and the use of computers in imaging and image analysis. These new technologies have now been applied to microbiological problems with resounding success. 相似文献
952.
Stromal cells mediate retinoid-dependent functions essential for renal development 总被引:13,自引:0,他引:13
Mendelsohn C Batourina E Fung S Gilbert T Dodd J 《Development (Cambridge, England)》1999,126(6):1139-1148
953.
Weising Kurt Fung Raymond W.M. Keeling D. Jeannette Atkinson Ross G. Gardner Richard C. 《Molecular breeding : new strategies in plant improvement》1997,3(2):159-160
Molecular Breeding - 相似文献
954.
955.
Fung MK Han HY Leung SC Cheung HW Cheung AL Wong YC Ling MT Wang X 《Journal of molecular biology》2008,381(1):24-34
MAD2 (mitotic arrest deficient 2) is a key regulator of mitosis. Recently, it had been suggested that MAD2-induced mitotic arrest mediates DNA damage response and that upregulation of MAD2 confers sensitivity to DNA-damaging anticancer drug-induced apoptosis. In this study, we report a potential novel role of MAD2 in mediating DNA nucleotide excision repair through physical interactions with two DNA repair proteins, XPD (xeroderma pigmentosum complementation group D) and ERCC1. First, overexpression of MAD2 resulted in decreased nuclear accumulation of XPD, a crucial step in the initiation of DNA repair. Second, immunoprecipitation experiments showed that MAD2 was able to bind to XPD, which led to competitive suppression of binding activity between XPD and XPA, resulting in the prevention of physical interactions between DNA repair proteins. Third, unlike its role in mitosis, the N-terminus domain seemed to be more important in the binding activity between MAD2 and XPD. Fourth, phosphorylation of H2AX, a process that is important for recruitment of DNA repair factors to DNA double-strand breaks, was suppressed in MAD2-overexpressing cells in response to DNA damage. These results suggest a negative role of MAD2 in DNA damage response, which may be accounted for its previously reported role in promoting sensitivity to DNA-damaging agents in cancer cells. However, the interaction between MAD2 and ERCC1 did not show any effect on the binding activity between ERCC1 and XPA in the presence or absence of DNA damage. Our results suggest a novel function of MAD2 by interfering with DNA repair proteins. 相似文献
956.
Anti-proliferative and pro-apoptotic effect of Smilax glabra Roxb. extract on hepatoma cell lines 总被引:3,自引:0,他引:3
Smilax glabra Roxb. (SGR) is the root of a traditional Chinese herb, referred to as tu fu ling in Chinese medicine. It is an inexpensive traditional Chinese medicine commonly used for the treatment of liver diseases, and a few studies have indicated that SGR has anti-hepatocarcinogenic and anti-cancer growth activities. In the current study, raw SGR plant was extracted with Accelerate Solvent Extractor, and the molecular mechanism by which S. glabra Roxb. extract (SGRE) has an anti-proliferative effect on the human hepatoma cell lines, HepG2 and Hep3B, was determined. We showed that SGRE inhibited HepG2 and Hep3B cell growth by causing cell-cycle arrest at either S phase or S/G2 transition and induced apoptosis, as evidenced by a DNA fragmentation assay. SGRE-induced apoptosis by alternation of mitochondrial transmembrane depolarization, release of mitochondrial cytochrome c, activation of caspase-3, and cleavage of poly(ADP-ribose) polymerase. The SGRE-mediated mitochondria-caspase dependent apoptotic pathway also involved activation of p38, JNK, and ERK mitogen-activated protein kinase signaling. Isometric compounds of astilbin (flavonoids) and smilagenin (saponin) have been identified as the main chemical constituents in SGRE by HPLC-MS/MS. These results have identified, for the first time, the biological activity of SGRE in HepG2 and Hep3B cells and should lead to further development of SGR for liver disease therapy. 相似文献
957.
The hepatocyte growth factor (HGF) receptor, Met, is frequently overexpressed in nasopharyngeal cancer (NPC). Here, we showed for the first time that human NPC cells with high Met expression were more sensitive to the cell motility and invasion effect of HGF. The downregulation of Met by small interfering RNA decreased tumor cell invasion/migration. HGF significantly increased matrix metalloproteinase-9 production. This was inhibited by blocking phosphatidylinositide 3-kinase (PI3K) and c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase signaling pathways. We also demonstrated that PI3K induced activation of JNK, with Akt as a potential point of this cross-talk. These results provide new insights into the molecular mechanism responsible for NPC progression and metastasis. 相似文献
958.
Sorensen B Rohde J Wang J Fung S Monzon K Chiou W Pan L Deng X Stolarik D Frevert EU Jacobson P Link JT 《Bioorganic & medicinal chemistry letters》2006,16(23):5958-5962
A series of potent and selective adamantane aminoamide 11-beta-HSD-1 inhibitors has been optimized. Chemically these studies were expedited by utilizing readily obtained amino acids as starting materials or an isocyanide multicomponent reaction. Structure-activity relationship studies resulted in the discovery of dual human and mouse 11-beta-HSD-1 potent and selective inhibitors like adamantane 11 and related compounds with high metabolic stability and robust pharmacokinetic profiles. 相似文献
959.
David T. Fung Vincent M. Wang Nelly Andarawis-Puri Jelena Basta-Pljakic Yonghui Li Damien M. Laudier Hui B. Sun Karl J. Jepsen Mitchell B. Schaffler Evan L. Flatow 《Journal of biomechanics》2010,43(2):274-279
This study describes the development and application of a novel rat patellar tendon model of mechanical fatigue for investigating the early in vivo response to tendon subfailure injury. Patellar tendons of adult female Sprague-Dawley rats were fatigue loaded between 1–35 N using a custom-designed loading apparatus. Patellar tendons were subjected to Low-, Moderate- or High-level fatigue damage, defined by grip-to-grip strain measurement. Molecular response was compared with that of a laceration-repair injury. Histological analyses showed that progression of tendon fatigue involves formation of localized kinked fiber deformations at Low damage, which increased in density with presence of fiber delaminations at Moderate damage, and fiber angulation and discontinuities at High damage levels. RT-PCR analysis performed at 1- and 3-day post-fatigue showed variable changes in type I, III and V collagen mRNA expression at Low and Moderate damage levels, consistent with clinical findings of tendon pathology and were modest compared with those observed at High damage levels, in which expression of all collagens evaluated were increased markedly. In contrast, only type I collagen expression was elevated at the same time points post-laceration. Findings suggest that cumulative fatigue in tendon invokes a different molecular response than laceration. Further, structural repair may not be initiated until reaching end-stage fatigue life, where the repair response may unable to restore the damaged tendon to its pre-fatigue architecture. 相似文献
960.