全文获取类型
收费全文 | 222篇 |
免费 | 20篇 |
国内免费 | 1篇 |
出版年
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 7篇 |
2016年 | 11篇 |
2015年 | 10篇 |
2014年 | 14篇 |
2013年 | 14篇 |
2012年 | 11篇 |
2011年 | 19篇 |
2010年 | 5篇 |
2009年 | 7篇 |
2008年 | 8篇 |
2007年 | 19篇 |
2006年 | 3篇 |
2005年 | 2篇 |
2004年 | 4篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 5篇 |
1994年 | 3篇 |
1992年 | 6篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1979年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有243条查询结果,搜索用时 15 毫秒
71.
Calcium activated neutral proteinase (mcalpain) activity was determined in brain and other tissue of rat. More than 60% of the brain mcalpain activity was present in the particulate fraction while only 30% was in cytosol. In contrast, particulate fractions of liver, kidney, muscle, and heart contained about 8–12% of tissue mcalpain activity while 88% was present in cytosol. Removal of the endogenous inhibitor calpastatin increased the tissue mcalpain activity severalfold. Triton X-100 and deoxycholate (DOC) stimulated the neural calpain activity by ten-fold while activity in non-neural tissue was unaffected. Incubation with other detergents, e.g. Triton N-57 and thioglucopyranoside, stimulated brain calpain activity five-fold while Brij-35 did not have any effect. Sodiumdodecylsulphate (SDS), on the other hand, inhibited the enzyme activity. Brain contained the lowest calpain activity compared to non-neural tissue. The calpain activity in muscle, kidney and heart was three-fold greater than liver. Immunoblot identification of the enzyme revealed that calpain was predominantly in the particulate fraction and less in cytosol of brain while it was present mainly in cytosol and less in the pellet fractions of non-neural tissue. 相似文献
72.
Synthesis of the trans 1-N-chrysenyl and 1-N-phenanthrenyl 3-acetoxy-4-phenyl-2-azetidinones has been achieved. Microwave-assisted reaction has proved useful in the synthesis of these compounds. Cell growth inhibition study has indicated selective anticancer activity against two leukemia and colon carcinoma cell lines. A mechanistic correlation of their anticancer activity has been described. Striking G2 blockade that is clearly distinct in cell cycle analysis and demonstrated only in sensitive cell lines has been observed. They do not induce apoptosis in sensitive or resistant lines. They also do not inhibit topoisomerases. Ames test has shown they are nonmutagenic. 相似文献
73.
In this study, we examine the clinical, neuroradiological, and immunohistochemical findings of a 51 year old white female who died 27 months after onset of acute multiple sclerosis despite treatment with interferon-, azathioprine, corticosteroids, and cyclophosphamide. Immunohistochemical studies revealed extensive gliosis and mononuclear phagocyte infiltration with corresponding upregulation of proinflammatory cytokines (eg. IFN-, TNF-). The significance of immunohistochemical findings with respect to clinical presentation is discussed. 相似文献
74.
Becker FF Mukhopadhyay C Hackfeld L Banik I Banik BK 《Bioorganic & medicinal chemistry》2000,8(12):1033-2699
Highly regioselective electrophilic substitution of dibenzofluorene was achieved and the nitro derivative was transformed to a variety of new anticancer agents. 相似文献
75.
A large number of diamides and diamines were synthesized using 6-amino chrysene and 1-amino pyrene as starting materials. A structure activity study with cis-platinum as internal control against animal and human tumor lines was carried out in vitro. This study indicated that the in vitro cytotoxicity toward these lines depends on the functionality present in the molecules. The diamino compounds were found to be more potent than the diamides, and these were equally active irrespective of the end heterocyclic group, whereas the activity of the diamides was strongly dependent on the terminal unit. In general, the diamides containing chrysene as the chromophore were more active than those with a pyrene ring. The size of the end heterocyclic ring, along with the nature of the spacer connecting the polycyclic ring to the heterocyclic ring, seemed to affect the biological activity in certain cell lines. Hemolysis experiments on a lead compound established that it had activities similar to those described for membrane-stabilizing agents. This agent also demonstrated the capacity to produce differentiation in leukemia cell lines. 相似文献
76.
Etheridge KT Banik SS Armbruster BN Zhu Y Terns RM Terns MP Counter CM 《The Journal of biological chemistry》2002,277(27):24764-24770
77.
78.
Rachel J. Dotson Seham M. Rabadi Elizabeth L. Westcott Stephen Bradley Sally V. Catlett Sukalyani Banik Jonathan A. Harton Chandra Shekhar Bakshi Meenakshi Malik 《The Journal of biological chemistry》2013,288(33):23844-23857
Francisella tularensis is an important human pathogen responsible for causing tularemia. F. tularensis has long been developed as a biological weapon and is now classified as a category A agent by the Centers for Disease Control because of its possible use as a bioterror agent. F. tularensis represses inflammasome; a cytosolic multi-protein complex that activates caspase-1 to produce proinflammatory cytokines IL-1β and IL-18. However, the Francisella factors and the mechanisms through which F. tularensis mediates these suppressive effects remain relatively unknown. Utilizing a mutant of F. tularensis in FTL_0325 gene, this study investigated the mechanisms of inflammasome repression by F. tularensis. We demonstrate that muted IL-1β and IL-18 responses generated in macrophages infected with F. tularensis live vaccine strain (LVS) or the virulent SchuS4 strain are due to a predominant suppressive effect on TLR2-dependent signal 1. Our results also demonstrate that FTL_0325 of F. tularensis impacts proIL-1β expression as early as 2 h post-infection and delays activation of AIM2 and NLRP3-inflammasomes in a TLR2-dependent fashion. An enhanced activation of caspase-1 and IL-1β observed in FTL_0325 mutant-infected macrophages at 24 h post-infection was independent of both AIM2 and NLRP3. Furthermore, F. tularensis LVS delayed pyroptotic cell death of the infected macrophages in an FTL_0325-dependent manner during the early stages of infection. In vivo studies in mice revealed that suppression of IL-1β by FTL_0325 early during infection facilitates the establishment of a fulminate infection by F. tularensis. Collectively, this study provides evidence that F. tularensis LVS represses inflammasome activation and that F. tularensis-encoded FTL_0325 mediates this effect. 相似文献
79.
Benjamin M. Johnson Faisal F. Y. Radwan Azim Hossain Bently P. Doonan Jessica D. Hathaway-Schrader Jason M. God Christina V. Voelkel-Johnson Narendra L. Banik Sakamuri V. Reddy Azizul Haque 《Journal of cellular biochemistry》2019,120(4):6264-6276
Though the current therapies are effective at clearing an early stage prostate cancer, they often fail to treat late-stage metastatic disease. We aimed to investigate the molecular mechanisms underlying the anticancer effects of a natural triterpenoid, ganoderic acid DM (GA-DM), on two human prostate cancer cell lines: the androgen-independent prostate carcinoma (PC-3), and androgen-sensitive prostate adenocarcinoma (LNCaP). Cell viability assay showed that GA-DM was relatively more toxic to LNCaP cells than to PC-3 cells (IC50s ranged 45-55 µM for PC-3, and 20-25 µM for LNCaP), which may have occurred due to differential expression of p53. Hoechst DNA staining confirmed detectable nuclear fragmentation in both cell lines irrespective of the p53 status. GA-DM treatment decreased Bcl-2 proteins while it upregulated apoptotic Bax and autophagic Beclin-1, Atg5, and LC-3 molecules, and caused an induction of both early and late events of apoptotic cell death. Biochemical analyses of GA-DM-treated prostate cancer cells demonstrated that caspase-3 cleavage was notable in GA-DM-treated PC-3 cells. Interestingly, GA-DM treatment altered cell cycle progression in the S phase with a significant growth arrest in the G2 checkpoint and enhanced CD4 + T cell recognition of prostate tumor cells. Mechanistic study of GA-DM-treated prostate cancer cells further demonstrated that calpain activation and endoplasmic reticulum stress contributed to cell death. These findings suggest that GA-DM is a candidate for future drug design for prostate cancer as it activates multiple pathways of cell death and immune recognition. 相似文献
80.