全文获取类型
收费全文 | 134篇 |
免费 | 12篇 |
国内免费 | 18篇 |
出版年
2023年 | 1篇 |
2022年 | 6篇 |
2021年 | 11篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2016年 | 6篇 |
2015年 | 7篇 |
2014年 | 8篇 |
2013年 | 12篇 |
2012年 | 10篇 |
2011年 | 9篇 |
2010年 | 13篇 |
2009年 | 6篇 |
2008年 | 10篇 |
2007年 | 2篇 |
2006年 | 2篇 |
2005年 | 3篇 |
2004年 | 1篇 |
2003年 | 2篇 |
2002年 | 7篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1988年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有164条查询结果,搜索用时 203 毫秒
21.
We have examined global chemical shift perturbations for aP2 ligand complexes and compared these with amide temperature coefficients. Hydrogen bond potential was monitored by amide chemical shift's temperature coefficient. Based on this information, we propose that the binding energy contribution can be spread out to multiple distant residues. For aP2, the ability of the receptor protein to change its hydrogen bond interactions in the beta-strands to accommodate different ligand scaffolds seems to make this receptor difficult for structure based drug design. While stabilization energy differential on hydrogen bonds is likely to be small for individual residues, the accumulative effect on multiple hydrogen bonds may have a dramatic impact on ligand affinity. 相似文献
22.
Tang H Kambris Z Lemaitre B Hashimoto C 《The Journal of biological chemistry》2006,281(38):28097-28104
The melanization reaction is used as an immune mechanism in arthropods to encapsulate and kill microbial pathogens. In Drosophila, the serpin Spn27A regulates melanization apparently by inhibiting the protease that activates phenoloxidase, the key enzyme in melanin synthesis. Here, we have described the genetic characterization of two immune inducible serine proteases, MP1 and MP2, which act in a melanization cascade regulated by Spn27A. MP1 is required to activate melanization in response to both bacterial and fungal infection, whereas MP2 is mainly involved during fungal infection. Pathogenic bacteria and fungi may therefore trigger two different melanization cascades that use MP1 as a common downstream protease to activate phenoloxidase. We have also shown that the melanization reaction activated by MP1 and MP2 plays an important role in augmenting the effectiveness of other immune reactions, thereby promoting resistance of Drosophila to microbial infection. 相似文献
23.
24.
Huaping Li Na Jiang Bihua Liang Qing Liu Erting Zhang Liqian Peng 《Redox report : communications in free radical research》2017,22(6):501-507
Objective: Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes.Methods: Human keratinocytes were pretreated with Pter (5 and 10?μM) for 24?h prior to UVB irradiation (300?mJ/cm2). Harvested cells were analyzed by MTT, DCFH-DA, comet, western blotting, luciferase promoter, small interference RNA transfection, and quantitative real-time polymerase chain reaction assay.Results: Pter significantly attenuated UVB-induced cell death and reactive oxygen species (ROS) generation, and effectively increased nuclear translocation of NF-E2-related factor-2 (Nrf2), expression of Nrf2-dependent antioxidant enzymes, and DNA repair activity. Moreover, the protective effects of Pter were abolished by small interference RNA-mediated Nrf2 silencing. Furthermore, Pter was also found to induce the phosphorylation of Nrf2 and the known phosphatidylinositol-3-kinase (PI3K) phosphorylated kinase, Akt. The specific inhibitor of PI3K, LY294002, successfully abrogated Pter-induced Nrf2 phosphorylation, activation of Nrf2-antioxidant response element pathway, ROS scavenging ability, and DNA repair activity.Conclusion: The present study indicated that Pter effectively protected against UVB-induced photodamage by increasing endogenous defense mechanisms, scavenging UVB-induced ROS, and aiding in damaged DNA repair through a PI3K-dependent activation of Nrf2/ARE pathway. 相似文献
25.
Huaping Mou Ping Guo Xiaoming Li Chuanli Zhang Jing Jiang Lishuai Wang 《Cell cycle (Georgetown, Tex.)》2017,16(14):1366-1375
Nitidine chloride (NC) has been reported to exert its anti-tumor activity in various types of human cancers. However, the molecular mechanism of NC-mediated tumor suppressive function is largely unclear. In the current study, we used several approaches such as MTT, FACS, RT-PCR, Western blotting analysis, invasion assay, transfection, to explore the molecular basis of NC-triggered anti-cancer activity. We found that NC inhibited cell growth, induced cell apoptosis, caused cell cycle arrest in ovarian cancer cells. Emerging evidence has demonstrated that Skp2 plays an important oncogenic role in ovarian cancer. Therefore, we also explored whether NC exerts its biologic function via downregulation of Skp2 in ovarian cancer cells. We observed that NC significantly inhibited the expression of Skp2 in ovarian cancer cells. Notably, overexpression of Skp2 abrogated the anti-cancer activity induced by NC in ovarian cancer cells. Consistently, downregulation of Skp2 expression enhanced the sensitivity of ovarian cancer cells to NC treatment. Thus, inactivation of Skp2 by NC could be a novel strategy for the treatment of human ovarian cancer. 相似文献
26.
27.
Yongjun Tang Chengping Hu Huaping Yang Liming Cao Yuanyuan Li Pengbo Deng Li Huang 《PloS one》2014,9(11)
Rnd3/RhoE is a small Rho GTPase involved in the regulation of different cell behaviors. Dysregulation of Rnd3 has been linked to tumorigenesis and metastasis. Lung cancers are the leading cause of cancer-related death in the West and around the world. The expression of Rnd3 and its ectopic role in non-small cell lung cancer (NSCLC) remain to be explored. Here, we reported that Rnd3 was down-regulated in three NSCLC cell lines: H358, H520 and A549. The down-regulation of Rnd3 led to hyper-activation of Rho Kinase and Notch signaling. The reintroduction of Rnd3 or selective inhibition of Notch signaling, but not Rho Kinase signaling, blocked the proliferation of H358 and H520 cells. Mechanistically, Notch intracellular domain (NICD) protein abundance in H358 cells was regulated by Rnd3-mediated NICD proteasome degradation. Rnd3 regulated H358 and H520 cell proliferation through a Notch1/NICD/Hes1 signaling axis independent of Rho Kinase. 相似文献
28.
29.
30.
【背景】生物受到温度胁迫时,热激蛋白被诱导并在短时间内大量产生,可以使受损的蛋白质恢复正常构象,增强生物对逆境胁迫的耐受性。【目的】初步探究草菇热激蛋白60(Vvhsp60)与低温耐受性的关系,为深入开展草菇不耐低温特性的遗传改良奠定理论基础。【方法】对Vvhsp60进行生物信息学分析,以低温敏感型草菇菌株V23及耐低温菌株VH3为实验材料,利用实时荧光定量PCR技术分析低温胁迫及热激诱导后在低温下草菇菌丝体中Vvhsp60基因的表达水平。【结果】草菇Vvhsp60编码蛋白不存在信号肽,不属于分泌蛋白,在线粒体和细胞质内发挥生物学作用,属于双向跨膜蛋白。低温处理显著提高了V23与VH3菌丝体中Vvhsp60基因的表达量,而且VH3中的表达量显著高于V23,推测Vvhsp60基因的表达量高可能有助于增强草菇对低温胁迫的耐受性。经热激处理后两菌株Vvhsp60基因的表达量显著高于各自未热激处理的对照组,表明热激处理可诱导Vvhsp60基因的表达。【结论】Vvhsp60与草菇低温耐受性相关,并且热激可以诱导Vvhsp60基因的表达。 相似文献