全文获取类型
收费全文 | 623篇 |
免费 | 35篇 |
专业分类
658篇 |
出版年
2023年 | 8篇 |
2022年 | 13篇 |
2021年 | 27篇 |
2020年 | 17篇 |
2019年 | 7篇 |
2018年 | 17篇 |
2017年 | 14篇 |
2016年 | 14篇 |
2015年 | 21篇 |
2014年 | 33篇 |
2013年 | 48篇 |
2012年 | 53篇 |
2011年 | 64篇 |
2010年 | 32篇 |
2009年 | 30篇 |
2008年 | 31篇 |
2007年 | 20篇 |
2006年 | 28篇 |
2005年 | 25篇 |
2004年 | 26篇 |
2003年 | 28篇 |
2002年 | 21篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 6篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1981年 | 7篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
排序方式: 共有658条查询结果,搜索用时 15 毫秒
161.
162.
Malla R Gopinath S Alapati K Gondi CS Gujrati M Dinh DH Mohanam S Rao JS 《PloS one》2010,5(10):e13731
Background
Glioma is the most commonly diagnosed primary brain tumor and is characterized by invasive and infiltrative behavior. uPAR and cathepsin B are known to be overexpressed in high-grade gliomas and are strongly correlated with invasive cancer phenotypes.Methodology/Principal Findings
In the present study, we observed that simultaneous downregulation of uPAR and cathepsin B induces upregulation of some pro-apoptotic genes and suppression of anti-apoptotic genes in human glioma cells. uPAR and cathepsin B (pCU)-downregulated cells exhibited decreases in the Bcl-2/Bax ratio and initiated the collapse of mitochondrial membrane potential. We also observed that the broad caspase inhibitor, Z-Asp-2, 6-dichlorobenzoylmethylketone rescued pCU-induced apoptosis in U251 cells but not in 5310 cells. Immunoblot analysis of caspase-9 immunoprecipitates for Apaf-1 showed that uPAR and cathepsin B knockdown activated apoptosome complex formation in U251 cells. Downregulation of uPAR and cathepsin B also retarded nuclear translocation and interfered with DNA binding activity of CREB in both U251 and 5310 cells. Further western blotting analysis demonstrated that downregulation of uPAR and cathepsin B significantly decreased expression of the signaling molecules p-PDGFR-β, p-PI3K and p-Akt. An increase in the number of TUNEL-positive cells, increased Bax expression, and decreased Bcl-2 expression in nude mice brain tumor sections and brain tissue lysates confirm our in vitro results.Conclusions/Significance
In conclusion, RNAi-mediated downregulation of uPAR and cathepsin B initiates caspase-dependent mitochondrial apoptosis in U251 cells and caspase-independent mitochondrial apoptosis in 5310 cells. Thus, targeting uPAR and cathepsin B-mediated signaling using siRNA may serve as a novel therapeutic strategy for the treatment of gliomas. 相似文献163.
Hari Raghu Sajani S. Lakka Christopher S. Gondi Sanjeeva Mohanam Dzung H. Dinh Meena Gujrati Jasti S. Rao 《PloS one》2010,5(8)
Background
In our earlier reports, we showed that downregulation of uPA and uPAR inhibited glioma tumor angiogenesis in SNB19 cells, and intraperitoneal injection of a hairpin shRNA expressing plasmid targeting uPA and uPAR inhibited angiogenesis in nude mice. The exact mechanism by which inhibition of angiogenesis takes place is not clearly understood.Methodology/Principal Findings
In the present study, we have attempted to investigate the mechanism by which uPA/uPAR downregulation by shRNA inhibits angiogenesis in endothelial and glioblastoma cell lines. uPA/uPAR downregulation by shRNA in U87 MG and U87 SPARC co-cultures with endothelial cells inhibited angiogenesis as assessed by in vitro angiogenesis assay and in vivo dorsal skin-fold chamber model in nude mice. Protein antibody array analysis of co-cultures of U87 and U87 SPARC cells with endothelial cells treated with pU2 (shRNA against uPA and uPAR) showed decreased angiogenin secretion and angiopoietin-1 as well as several other pro-angiogenic molecules. Therefore, we investigated the role of angiogenin and found that nuclear translocation, ribonucleolytic and 45S rRNA synthesis, which are all critical for angiogenic function of angiogenin, were significantly inhibited in endothelial cells transfected with uPA, uPAR and uPA/uPAR when compared with controls. Moreover, uPA and uPAR downregulation significantly inhibited the phosphorylation of Tie-2 receptor and also down regulated FKHR activation in the nucleus of endothelial cells via the GRB2/AKT/BAD pathway. Treatment of endothelial cells with ruPA increased angiogenin secretion and angiogenin expression as determined by ELISA and western blotting in a dose-dependent manner. The amino terminal fragment of uPA down regulated ruPA-induced angiogenin in endothelial cells, thereby suggesting that uPA plays a critical role in positively regulating angiogenin in glioblastoma cells.Conclusions/Significance
Taken together, our results suggest that uPA/uPAR downregulation suppresses angiogenesis in endothelial cells induced by glioblastoma cell lines partially by downregulation of angiogenin and by inhibition of the angiopoietin-1/AKT/FKHR pathway. 相似文献164.
Molecular Biology Reports - Coriander (Coriandrum sativum L.) is well known vegetable and spice crop grown globally for its leaves and seeds. Stem gall (Protomyces macrosporus L.) is a fungal... 相似文献
165.
166.
Waterlogging induced oxidative stress and antioxidant activity in pigeonpea genotypes 总被引:2,自引:0,他引:2
D. Kumutha K. Ezhilmathi R. K. Sairam G. C. Srivastava P. S. Deshmukh R. C. Meena 《Biologia Plantarum》2009,53(1):75-84
The objective of this study was to examine the role of antioxidant enzymes in waterlogging tolerance of pigeonpea (Cajanus cajan L. Halls) genotypes ICP 301 (tolerant) and Pusa 207 (susceptible). Waterlogging resulted in visible yellowing and senescence
of leaves, decrease in leaf area, dry matter, relative water content and chlorophyll content in leaves, and membrane stability
index in roots and leaves. The decline in all parameters was greater in Pusa 207 than ICP 301. Oxidative stress in the form
of superoxide radical, hydrogen peroxide and thiobarbituric acid reactive substances (TBARS) contents initially decreased,
however at 4 and 6 d of waterlogging it increased over control plants, probably due to activation of DPI-sensitive NADPH-oxidase.
Antioxidant enzymes such as superoxide dismutase, ascorbate peroxidase, glutathione reductase and catalase also increased
under waterlogging. The comparatively greater antioxidant enzyme activities resulting in less oxidative stress in ICP 301
could be one of the factor determining its higher tolerance to flooding as compared to Pusa 207. This study is the first to
conclusively prove that waterlogging induced increase in ROS is via NADPH oxidase. 相似文献
167.
Nikita P. Lotlikar Samir R. Damare Ram Murti Meena P. Linsy Brenda Mascarenhas 《Indian journal of microbiology》2018,58(2):182-192
Chromium (Cr) released from industrial units such as tanneries, textile and electroplating industries is detrimental to the surrounding ecosystems and human health. The focus of the present study was to check the Cr(VI) removal efficiency by marine-derived fungi from liquid broth. Amongst the three Cr(VI) tolerant isolates, #NIOSN-SK56-S19 (Aspergillus sydowii) showed Cr-removal efficiency of 0.01 mg Cr mg?1 biomass resulting in 26% abatement of total Cr with just 2.8 mg of biomass produced during the growth in 300 ppm Cr(VI). Scanning Electron Microscopy revealed aggregation of mycelial biomass with exopolysaccharide, while Electron Dispersive Spectroscopy showed the presence of Cr2O3 inside the biomass indicating presence of active Cr(VI) removal mechanisms. This was further supported when the Cr(VI) removal was monitored using DPC (1,5-diphenylcarbazide) method. The results of this study point to the potential of marine-derived fungal isolates for Cr(VI) removal. 相似文献
168.
Chauhan M Balakrishnan M Yallampalli U Endsley J Hankins GD Theiler R Yallampalli C 《Biology of reproduction》2011,85(6):1232-1239
Adrenomedullin 2 (ADM2), also referred to as intermedin (IMD), is expressed in trophoblast cells in human placenta and enhances the invasion and migration of first-trimester HTR-8SV/neo cells. Further infusion of ADM2 antagonist in pregnant rat causes fetoplacental growth restriction, suggesting a role for ADM2 in maintaining a successful pregnancy. This study was undertaken to assess whether ADM2 protein is present in decidual tissue and colocalized with HLA-G-positive cytotrophoblast cells and natural killer cells; to assess whether ADM2 regulates expression of HLA-G in trophoblast cells; and to identify whether mitogen-activated protein kinase (MAPK) signaling pathway is involved in ADM2-induced trophoblast cell invasion and migration. Using immunohistochemical methods and RT-PCR, this study shows that ADM2 protein is colocalized with HLA-G-expressing cytotrophoblast cells as well as with NCAM1 (CD56) immunoreactivity in human first-trimester decidual tissue, and that ADM2 mRNA is expressed in peripheral blood natural killer cells. Further, ADM2 dose dependently increases the expression of HLA-G antigen in HTR-8SV/neo cells as well as in term placental villi explants, suggesting involvement of ADM2 in the regulation of HLA-G in trophoblast cells. In addition, interference with the activity of RAF and MAPK3/1 by their inhibitors, manumycin and U0126, respectively, reduces ADM2-induced HTR-8SV/neo cell invasion and migration. In summary, this study suggests a potential involvement for ADM2 in regulating HLA-G antigen at the maternal-fetal interface in human pregnancy and facilitating trophoblast invasion and migration via MAPK3/1 phosphorylation. 相似文献
169.
Media from Rhabdomyosarcoma and Neuroblastoma Cell Cultures Stimulate in Vitro Aggregation and Fibrillization of Amyloid Beta-Protein 总被引:3,自引:0,他引:3
Chauhan Abha Chauhan Ved P. S. Rubenstein Richard Wegiel Jerzy Wisniewski Henryk M. 《Neurochemical research》1997,22(2):227-232
In vitro aggregation and fibrillization of synthetic amyloid beta-protein A 1–40 was assessed in the conditioned media from rhabdomyosarcoma (CRL 1598, HTB 82, HTB 153, CCL 136), adenocarcinoma (CCL 218), neuroblastoma (SY5Y), and COS cells cultured in the absence and presence of 10% heat-inactivated fetal bovine serum (FBS). The aggregation and formation of cross -pleated sheet structures in A was quantitated by Thioflavin T (ThT) fluorescence spectroscopy, while the morphology of A fibrils was examined in negative staining in the electronmicroscope (EM). In cultures supplemented with 10% FBS, the conditioned media from CRL 1598, HTB 82, CCL 218, and SY5Y cell cultures stimulated A aggregation in a time-dependent manner as compared to that of control (serum-containing medium that had not been exposed to cells). The order of stimulation was SY5Y > CRL 1598 HTB 82 > CCL 218, and the stimulation was higher in 2 week cultures than in 1 week cultures. Similar studies using media from HTB 153, CCL 136 and COS cell cultures showed no effect on A 1–40 aggregation. In serum-free cell cultures, only media from SY5Y and CRL 1598 could promote significant aggregation of A 1–40. Negative staining in EM revealed A fibril formation only with conditioned media from SY5Y and CRL 1598 cultured under serum free conditions; no A fibrils were noticed in media from cell cultures supplemented with 10% FBS. We propose that both the SY5Y neuroblastoma cell line and the CRL 1598 rhabdomyosarcoma cell line may serve as experimental models for in vitro studies of extracellular aggregation and fibrillization of A-protein in cell cultures, while rhabdomyosarcoma HTB 82 and adenocarcinoma CCL 218 may be models for study of A aggregation only. 相似文献
170.
Narasimhan B Kumari M Jain N Dhake A Sundaravelan C 《Bioorganic & medicinal chemistry letters》2006,16(18):4951-4958
The antimicrobial activity of the N-[5-(2-furanyl)-2-methyl-4-oxo-4H-theino[2,3-d]pyrimidin-3-y1]-carboxamides and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones was correlated with different topological indices using Hansch analysis. Good correlations were obtained through a simple regression equation with third order molecular connectivity index (3chi). The developed QSAR models were crossvalidated by leave-one-out technique. 相似文献