全文获取类型
收费全文 | 162篇 |
免费 | 19篇 |
国内免费 | 9篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 8篇 |
2014年 | 9篇 |
2013年 | 6篇 |
2012年 | 9篇 |
2011年 | 7篇 |
2010年 | 13篇 |
2009年 | 5篇 |
2008年 | 5篇 |
2007年 | 10篇 |
2006年 | 9篇 |
2005年 | 4篇 |
2004年 | 5篇 |
2003年 | 5篇 |
2002年 | 7篇 |
2001年 | 11篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1962年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有190条查询结果,搜索用时 18 毫秒
21.
Shin-Ru Shih Tzu-Yun Chu Gadarla Randheer Reddy Sung-Nain Tseng Hsiun-Ling Chen Wen-Fang Tang Ming-sian Wu Jiann-Yih Yeh Yu-Sheng Chao John TA Hsu Hsing-Pang Hsieh Jim-Tong Horng 《Journal of biomedical science》2010,17(1):13
Background
Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals.Methods
We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle.Results
The 50% effective inhibitory concentration (IC50) of BPR1P0034 was 0.42 ± 0.11 μM, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus.Conclusions
To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-μM) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent. 相似文献22.
23.
24.
25.
Chia-Chun Yu Shih-Ping Liu Jui-Ling Hsu John TA Hsu Konstantin V Kudryavtsev Jih-Hwa Guh 《Journal of biomedical science》2015,22(1)
Background
Hormone-refractory prostate cancer (HRPC), which is resistant to hormone therapy, is a major obstacle in clinical treatment. An approach to inhibit HRPC growth and ultimately to kill cancers is highly demanded.Results
KUD773 induced the anti-proliferative effect and subsequent apoptosis in PC-3 and DU-145 (two HRPC cell lines); whereas, it showed less active in normal prostate cells. Further examination showed that KUD773 inhibited tubulin polymerization and induced an increase of mitotic phosphoproteins and polo-like kinase 1 (PLK1) phosphorylation, indicating a mitotic arrest of the cell cycle through an anti-tubulin action. The kinase assay demonstrated that KUD773 inhibited Aurora A activity. KUD773 induced an increase of Cdk1 phosphorylation at Thr161 (a stimulatory phosphorylation site) and a decrease of phosphorylation at Tyr15 (an inhibitory phosphorylation site), suggesting the activation of Cdk1. The data were substantiated by an up-regulation of cyclin B1 (a Cdk1 partner). Furthermore, KUD773 induced the phosphorylation and subsequent down-regulation of Bcl-2 and activation of caspase cascades.Conclusions
The data suggest that KUD773 induces apoptotic signaling in a sequential manner. It inhibits tubulin polymerization associated with an anti-Aurora A activity, leading to Cdk1 activation and mitotic arrest of the cell cycle that in turn induces Bcl-2 degradation and a subsequent caspase activation in HRPCs. 相似文献26.
铅锌镉联合染毒及营养干预对大鼠血液系统的影响研究 总被引:1,自引:0,他引:1
目的:了解铅锌镉联合染毒对大鼠血液系统的影响及营养干预对其损伤的修复作用。方法:选择SPF级初断乳Wistar大鼠72只,随机分为对照组、染毒组和干预组,分别采用生理盐水、铅锌镉联合染毒液及染毒后以营养干预液灌胃28天和56天之后,检测其血液系统中五元素和血细胞的指标。结果:染毒组较对照组大鼠血铜、血锌含量高,血钙含量低于对照组,差异均有统计学意义(P<0.05);染毒组血铜含量高于干预组,血钙含量低于干预组,差异均有统计学意义(P<0.05);干预组红细胞(RBC)计数、血红蛋白(Hb)、血细胞比容(HCT)均高于染毒组,差异均有统计学意义(P<0.05);对照组白细胞(WBC)计数高于染毒组、干预组,差异均有统计学意义(P<0.05)。结论:铅镉对大鼠血铜、血钙、血锌水平有影响;综合营养干预对重金属元素造成的血液系统损伤有明显的拮抗作用,对血液系统有一定的保护及修复作用。 相似文献
27.
对κ-卡拉胶进行酸降解得到三种卡拉胶低聚糖,并进一步琥珀酰基化得到分子量分别为2720、4000和5960的κ-卡拉胶琥珀酰衍生物(A、B和C)。对产物进行FT-IR表征,并测得其琥珀酰基取代度(DS)分别为0.61、0.29和0.83。检测了三种κ-卡拉胶琥珀酰衍生物对超氧阴离子自由基O2.-、DPPH自由基、羟基自由基.OH以及过氧化氢的清除活性。结果表明:随着取代度的增加,其清除超氧阴离子自由基O2.-和DPPH自由基的能力增强;随着分子量的增加,其清除羟基自由基.OH和过氧化氢的能力增强。这可能与衍生物的羟基含量、取代基团的性质以及取代度等因素有关。 相似文献
28.
29.
Michael D Kennedy Mark J Haykowsky Carol A Boliek Ben TA Esch Jessica M Scott Darren ER Warburton 《Dynamic medicine : DM》2006,5(1):8
Background
Near infrared spectroscopy (NIRS) is used to assess muscle oxygenation (MO) within skeletal muscle at rest and during aerobic exercise. Previous investigations have used a single probe placement to measure MO during various forms of exercise. However, regional MO differences have been shown to exist within the same muscle which suggests that different areas of the same muscle may have divergent MO. Thus, the aim of this study was to examine whether regional differences in MO exist within the same muscle during different types of incremental (rest, 25, 50, 75, 100 % of maximum) exercise (1 leg knee extension (KE), 2 leg KE, or cycling).Methods
Nineteen healthy active males (Mean ± SD: Age 27 ± 4 yrs; VO2max: 55 ± 11 mL/kg/min) performed incremental exercise to fatigue using each mode of exercise. NIRS probes were placed on the distal and proximal portion of right leg vastus lateralis (VL). Results were analyzed with a 3-way mixed model ANOVA (probe × intensity × mode).Results
Differences in MO exist within the VL for each mode of exercise, however these differences were not consistent for each level of intensity. Comparison of MO revealed that the distal region of VL was significantly lower throughout KE exercise (1 leg KE proximal MO – distal MO = 9.9 %; 2 leg KE proximal MO – distal MO = 13 %). In contrast, the difference in MO between proximal and distal regions of VL was smaller in cycling and was not significantly different at heavy workloads (75 and 100 % of maximum).Conclusion
MO is different within the same muscle and the pattern of the difference will change depending on the mode and intensity of exercise. Future investigations should limit conclusions on MO to the area under assessment as well as the type and intensity of exercise employed.30.
David A. Mead Susan Lucas Alex Copeland Alla Lapidus Jan-Feng Cheng David C. Bruce Lynne A. Goodwin Sam Pitluck Olga Chertkov Xiaojing Zhang John C. Detter Cliff S. Han Roxanne Tapia Miriam Land Loren J. Hauser Yun-juan Chang Nikos C. Kyrpides Natalia N. Ivanova Galina Ovchinnikova Tanja Woyke Catherine Brumm Rebecca Hochstein Thomas Schoenfeld Phillip Brumm 《Standards in genomic sciences》2012,6(3):381-400