全文获取类型
收费全文 | 419篇 |
免费 | 30篇 |
国内免费 | 67篇 |
出版年
2023年 | 6篇 |
2022年 | 13篇 |
2021年 | 25篇 |
2020年 | 27篇 |
2019年 | 22篇 |
2018年 | 20篇 |
2017年 | 17篇 |
2016年 | 28篇 |
2015年 | 41篇 |
2014年 | 42篇 |
2013年 | 40篇 |
2012年 | 57篇 |
2011年 | 28篇 |
2010年 | 17篇 |
2009年 | 15篇 |
2008年 | 20篇 |
2007年 | 24篇 |
2006年 | 17篇 |
2005年 | 7篇 |
2004年 | 10篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 7篇 |
1994年 | 1篇 |
1993年 | 4篇 |
1992年 | 1篇 |
1991年 | 2篇 |
排序方式: 共有516条查询结果,搜索用时 15 毫秒
1.
2.
3.
4.
5.
Jiao Hu Zenglei Hu Yiqun Mo Qiwen Wu Zhu Cui Zhiqiang Duan Junqing Huang Hongzhi Chen Yuxin Chen Min Gu Xiaoquan Wang Shunlin Hu Huimou Liu Wenbo Liu Xiaowen Liu Xiufan Liu 《Journal of virology》2013,87(20):11063-11075
Most highly pathogenic avian influenza A viruses cause only mild clinical signs in ducks, serving as an important natural reservoir of influenza A viruses. However, we isolated two H5N1 viruses that are genetically similar but differ greatly in virulence in ducks. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly pathogenic, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is low pathogenic. To determine the genetic basis for the high virulence of CK10 in ducks, we generated a series of single-gene reassortants between CK10 and GS10 and tested their virulence in ducks. Expression of the CK10 PA or hemagglutinin (HA) gene in the GS10 context resulted in increased virulence and virus replication. Conversely, inclusion of the GS10 PA or HA gene in the CK10 background attenuated the virulence and virus replication. Moreover, the PA gene had a greater contribution. We further determined that residues 101G and 237E in the PA gene contribute to the high virulence of CK10. Mutations at these two positions produced changes in virulence, virus replication, and polymerase activity of CK10 or GS10. Position 237 plays a greater role in determining these phenotypes. Moreover, the K237E mutation in the GS10 PA gene increased PA nuclear accumulation. Mutant GS10 viruses carrying the CK10 HA gene or the PA101G or PA237E mutation induced an enhanced innate immune response. A sustained innate response was detected in the brain rather than in the lung and spleen. Our results suggest that the PA and HA gene-mediated high virus replication and the intense innate immune response in the brain contribute to the high virulence of H5N1 virus in ducks. 相似文献
6.
Yitao Wang Dong Xu Xiao Fan Xiaowen Zhang Naihao Ye Wenqi Wang Yuze Mao Shanli Mou Shaona Cao 《Journal of applied phycology》2013,25(2):631-637
In order to illustrate the physiological variation of different generations and different thallus parts of Saccharina japonica, physiological parameters such as maximum and effective PSII photochemical efficiency, nutrient uptake, and elemental composition were determined in the laboratory. Photosynthetic analysis in different generations indicated that, although gametophytes had higher pigment contents than the sporophyte, they had lower values of F v/F m and ΔF/F′m. The highest Chl a/Chl c ratio was found in sporophyte generation (3.98?±?0.01) and in the basal part of fresh thallus (2.66?±?0.02). The sporophyte had significantly higher values of nitrate uptake but lower values of phosphorus uptake than the gametophytes. The contents of nitrogen and carbon as well as C/N in gametophytes were significantly higher than those in sporophytes. In addition, the basal part of the S. japonica thallus had the highest C content (22.31?±?1.50 %) but the lowest N content (2.02?±?0.16 %), as well as the highest value of C/N (11.02?±?0.34). 相似文献
7.
Xiaowen Yu Chunmei Li Weiling Hong Weihua Pan Jianping Xie 《Cellular signalling》2013,25(5):1272-1278
Autophagy is a cellular homeostasis mechanism to eliminate unwanted or excessive organelles, or for the turnover of long-life cytosolic macromolecules. During Mycobacterium tuberculosis infection, autophagy represents not only an antimicrobial mechanism for the clearance of the intracellular pathogen, but also prevents excessive inflammation, avoiding the adverse effects on host. Here we focus on the anti-tuberculosis autophagy and signal pathways involved, and attempt to depict an integrative map of the interaction between autophagy and cytokine, ROS production, vitamin D, and inflammatory response. Novel autophagy-based therapy is also summarized. This integrative insight might add some novel thoughts for better tuberculosis medications. 相似文献
8.
Mingsong Kang Ya-Ping Ko Xiaowen Liang Caná L. Ross Qing Liu Barbara E. Murray Magnus H??k 《The Journal of biological chemistry》2013,288(28):20520-20531
Members of a family of collagen-binding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) from Gram-positive bacteria are established virulence factors in several infectious diseases models. Here, we report that these adhesins also can bind C1q and act as inhibitors of the classical complement pathway. Molecular analyses of Cna from Staphylococcus aureus suggested that this prototype MSCRAMM bound to the collagenous domain of C1q and interfered with the interactions of C1r with C1q. As a result, C1r2C1s2 was displaced from C1q, and the C1 complex was deactivated. This novel function of the Cna-like MSCRAMMs represents a potential immune evasion strategy that could be used by numerous Gram-positive pathogens. 相似文献
9.
Qiao Sun Yiwu Yao Chunping Liu Hua Li Hequan Yao Xiaowen Xue Jinsong Liu Zhengchao Tu Sheng Jiang 《Bioorganic & medicinal chemistry letters》2013,23(11):3295-3299
We report the design, synthesis, and biological evaluation of a new series of HDAC1 inhibitors using click chemistry. Compound 17 bearing a phenyl ring at meta-position was identified to show much better selectivity for HDAC1 over HDAC7 than SAHA. The compond 17 also showed better in vitro anticancer activities against several cancer cell lines than that of SAHA. This work could serve as a foundation for further exploration of selective HDAC inhibitors using the compound 17 molecular scaffold. 相似文献
10.
Bohong Liao Lingrong Peng Jin Zhou Huiting Mo Jialan Zhao Zike Yang Xiaowen Guo Peiquan Zhang Xin Zhang Zhibo Zhu 《化学与生物多样性》2019,16(5)
Human nasopharyngeal carcinoma is a common head and neck malignancy with high incidence in Southeast Asia and Southern China. It is necessary to develop safe, effective and inexpensive anticancer agents to improve the therapeutics of patients with nasopharyngeal carcinoma. A series of small molecular compounds based on 6‐(pyrimidin‐4‐yl)‐1H‐indazole were synthesized and evaluated for antiproliferative activities against human nasopharyngeal carcinoma cell lines SUNE1. Compounds 6b , 6c , 6e and 6l showed potent antiproliferative activities similar to positive control drug cisplatin in vitro with lower nephrotoxicity than it. N‐[4‐(1H‐Indazol‐6‐yl)pyrimidin‐2‐yl]benzene‐1,3‐diamine ( 6l ) was selected for further study. It was found that 6l induced mitochondria‐mediated apoptosis and G2/M phase arrest in SUNE1 cells. Furthermore, compound 6l at 10 mg/kg can suppress the growth of an implanted SUNE1 xenograft with a TGI% (tumor growth inhibition) value of 50 % and did not cause serious side effects in BALB/c nude mice. This study suggests that 6‐(pyrimidin‐4‐yl)‐1H‐indazole derivatives are a series of small molecule compounds with anti‐nasopharyngeal carcinoma activities. 相似文献