全文获取类型
收费全文 | 152篇 |
免费 | 10篇 |
出版年
2024年 | 2篇 |
2023年 | 4篇 |
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 11篇 |
2012年 | 16篇 |
2011年 | 18篇 |
2010年 | 9篇 |
2009年 | 6篇 |
2008年 | 2篇 |
2007年 | 8篇 |
2006年 | 9篇 |
2005年 | 6篇 |
2004年 | 4篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有162条查询结果,搜索用时 515 毫秒
71.
72.
Haridas D Chakraborty S Ponnusamy MP Lakshmanan I Rachagani S Cruz E Kumar S Das S Lele SM Anderson JM Wittel UA Hollingsworth MA Batra SK 《PloS one》2011,6(10):e26839
MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease. 相似文献
73.
N.S.H.N. Moorthy Natércia F. Brás Maria J. Ramos Pedro A. Fernandes 《Bioorganic & medicinal chemistry》2012,20(24):6945-6959
Virtual screening and QSAR analysis were carried out to investigate the binding features of (2R, 3R, 4S)-2-aminomethylpyrrolidine 3,4-diol and the functionalized pyrrolidine derivatives to the α-mannosidase I and II enzymes. The QSAR models (possessed considerable R2, Q2 values, etc.) suggested that the presence of polar property on the vdW surface (vsurf_W, vsurf_Wp, etc.) of the molecules is important along with the presence of aromatic rings (opr_violation) in the molecules (which also provide hydrophobicity to the molecules). The docking study performed on α-mannosidase I and II enzymes pointed that the main interactions occur by hydrogen bonds, hydrophobic π–π stacking contacts and salt bridges with the cation calcium (for α-mannosidase I) and close interaction with zinc ion (α-mannosidase II), respectively. The bond flexibility orientates the aromatic ring in the molecules toward the hydrophobic cavity for π–π stacking contacts with the aromatic amino acids (Phe528, Phe329 and Phe659 for α-mannosidase I and Trp95, Tyr269, Phe312, Tyr102 for α-mannosidase II). The pharmacophore analysis also supports the results derived from the docking and QSAR studies. Our results suggest that the best compound to inhibit both classes of α-mannosidase is the compound 30, which may be used to design similar and better inhibitors to next generation drugs. 相似文献
74.
How a single residue in individual β-thymosin/WH2 domains controls their functions in actin assembly
Didry D Cantrelle FX Husson C Roblin P Moorthy AM Perez J Le Clainche C Hertzog M Guittet E Carlier MF van Heijenoort C Renault L 《The EMBO journal》2012,31(4):1000-1013
β-Thymosin (βT) and WH2 domains are widespread, intrinsically disordered actin-binding peptides that display significant sequence variability and different regulations of actin self-assembly in motile and morphogenetic processes. Here, we reveal the structural mechanisms by which, in their 1:1 stoichiometric complexes with actin, they either inhibit assembly by sequestering actin monomers like Thymosin-β4, or enhance motility by directing polarized filament assembly like Ciboulot βT. We combined mutational, functional or structural analysis by X-ray crystallography, SAXS (small angle X-ray scattering) and NMR on Thymosin-β4, Ciboulot, TetraThymosinβ and the long WH2 domain of WASP-interacting protein. The latter sequesters G-actin with the same molecular mechanisms as Thymosin-β4. Functionally different βT/WH2 domains differ by distinct dynamics of their C-terminal half interactions with G-actin pointed face. These C-terminal interaction dynamics are controlled by the strength of electrostatic interactions with G-actin. At physiological ionic strength, a single salt bridge with actin located next to their central LKKT/V motif induces G-actin sequestration in both isolated long βT and WH2 domains. The results open perspectives for elucidating the functions of βT/WH2 domains in other modular proteins. 相似文献
75.
Farshid Dayyani Nila U. Parikh Andreas S. Varkaris Jian H. Song Shhyam Moorthy Tanushree Chatterji Sankar N. Maity Adam R. Wolfe Joan M. Carboni Marco M. Gottardis Christopher J. Logothetis Gary E. Gallick 《PloS one》2012,7(12)
Background
Treatment of metastatic prostate cancer (PCa) with single agents has shown only modest efficacy. We hypothesized dual inhibition of different pathways in PCa results in improved tumor inhibition. The Src family kinases (SFK) and insulin-like growth factor-1 (IGF-1) signaling axes are aberrantly activated in both primary PCa and bone metastases and regulate distinct and overlapping functions in PCa progression. We examined the antitumor effects of combined inhibition of these pathways.Materials and Methods
Src andIGF-1 receptor (IGF-1R) inhibition was achieved in vitro by short hairpin (sh)RNA and in vitro and in vivo by small molecule inhibitors (dasatinib and BMS-754807, against SFK and IGF-1R/Insulin Receptor(IR), respectively).Results
In vitro, inhibition of IGF-1 signaling affected cell survival and proliferation. SFK blockade alone had modest effects on proliferation, but significantly enhanced the IGF-1R blockade. These findings correlated with a robust inhibition of IGF-1-induced Akt1 phophorylation by dasatinib, whereas Akt2 phosphorylation was SFK independent and only inhibited by BMS-754807. Thus, complete inhibition of both Akt genes, not seen by either drug alone, is likely a major mechanism for the decreased survival of PCa cells. Furthermore, dasatinib and BMS-754807 inhibited in vivo growth of the primary human xenograft MDA PCa 133, with corresponding inhibition of Akt in tumors. Also, both orthotopic and intratibial tumor growth of PC-3 cells were more potently inhibited by dual SFK and IGF-1R/IR blockade compared to either pathway alone, with a corresponding decrease in bone turnover markers.Conclusions
Dual IGF-1R/IR and SFK inhibition may be a rational therapeutic approach in PCa by blocking both independent and complementary processes critical to tumor growth. 相似文献76.
Ramar Perumal Samy Peramaiyan Rajendran Feng Li Narayana Moorthy Anandi Bradley G. Stiles Savarimuthu Ignacimuthu Gautam Sethi Vincent T. K. Chow 《PloS one》2012,7(12)
Breast cancer is the most common cancer among women. To date, improvements in hormonal and cytotoxic therapies have not yet led to a sustained remission or cure. In the present study, we investigated the in vitro and in vivo antitumor activities of a novel Calotropis procera protein (CP-P) isolated from root bark. CP-P protein inhibited the proliferation and induced apoptosis of breast cancer cells through the suppression of nuclear factor kappaB (NF-kB) activation. CP-P, when administered individually or in combination with cyclophosphamide (CYC, 0.2 mg/kg) to rats with 7, 12-dimethyl benz(a)anthracene (DMBA)-induced breast cancer decreased tumor volume significantly without affecting the body weight. To elucidate the anticancer mechanism of CP-P, antioxidant activities such as superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and non-enzymatic antioxidant - reduced glutathione (GSH), vitamin E and C generation in the breast were analyzed by various assays. SOD, CAT, GST, GSH, vitamin E and C levels were high in combination-treated groups (CP-P+CYC) versus the CYC alone-treated groups. Also, the combination was more effective in down-regulating the expression of NF-kB-regulated gene products (cyclin D1 and Bcl-2) in breast tumor tissues. Our findings indicate that CP-P possesses significant antitumor activity comparable to a commonly used anticancer drug, cyclophosphamide, and may form the basis of a novel therapy for breast cancer. 相似文献
77.
Stanley D. Chamberlain Joseph W. Wilson Felix Deanda Samarjit Patnaik Anikó M. Redman Bin Yang Lisa Shewchuk Peter Sabbatini M. Anthony Leesnitzer Arthur Groy Charity Atkins Roseanne Gerding Anne M. Hassell Huangshu Lei Robert A. Mook Ganesh Moorthy Jason L. Rowand Kirk L. Stevens Rakesh Kumar J. Brad Shotwell 《Bioorganic & medicinal chemistry letters》2009,19(2):469-473
The evaluation of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines as inhibitors of the IGF-1R (IGF-IR) receptor tyrosine kinase is reported. Examples demonstrate nanomolar potencies in in vitro enzyme and mechanistic cellular assays as well as promising in vivo pharmacokinetics in rat. 相似文献
78.
Stanley D. Chamberlain Anikó M. Redman Joseph W. Wilson Felix Deanda J. Brad Shotwell Roseanne Gerding Huangshu Lei Bin Yang Kirk L. Stevens Anne M. Hassell Lisa M. Shewchuk M. Anthony Leesnitzer Jeffery L. Smith Peter Sabbatini Charity Atkins Arthur Groy Jason L. Rowand Rakesh Kumar Robert A. Mook Ganesh Moorthy Samarjit Patnaik 《Bioorganic & medicinal chemistry letters》2009,19(2):360-364
The SAR of C5′ functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays. 相似文献
79.
Processing of the Epstein-Barr virus-encoded latent membrane protein p63/LMP. 总被引:6,自引:5,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We have analyzed the processing of the Epstein-Barr virus-encoded latent membrane protein (p63/LMP) in lymphoblastoid cell lines, Burkitt's lymphoma cell lines, and rodent fibroblasts transfected with the p63/LMP gene. Pulse-chase analysis by immunoprecipitation, under denaturing conditions, reveals a half-life of 2 h. This is due to turnover in the plasma membrane with cleavage of the protein, resulting in a 25,000-molecular-weight (p25) fragment derived from the carboxy-terminal portion of LMP. This fragment is rich in proline and acidic amino acids and sheds into the cytoplasm, where it appears to accumulate, being present in a six- to sevenfold molar excess over p63/LMP in immunoprecipitation analyses. p25 is, like p63/LMP, also phosphorylated (pp25) on serine and threonine residues, in the same ratio and to approximately the same extent as the intact p63/LMP molecule. Amino acid sequence analysis and carboxy-terminal labeling suggest that p25 is derived through a single cleavage adjacent to the sequence LGAPGGGPDNGPQDPD. 相似文献
80.
Attenuation of N-nitrosodiethylamine-induced hepatocellular carcinogenesis by a novel flavonol-Morin
Sivaramakrishnan V Shilpa PN Praveen Kumar VR Niranjali Devaraj S 《Chemico-biological interactions》2008,171(1):79-88
Morin (3,5,7,2′,4′-pentahydroxyflavone), a plant-derived flavonoid belonging to the subclass of flavonol is believed to play a role in chemoprevention and cancer chemotherapy. In this study, we found that the cotreatment of morin (500 ppm in diet) for 16 weeks to N-nitosodiethylamine-induced (200 mg/kg bodyweight in drinking water) rats provides protection against the oxidative stress caused by the carcinogen and thereby prevents hepatocellular carcinogenesis. On administration of the carcinogen, the level of lipid peroxidation increased markedly, but was found to be significantly lowered by morin treatment. On the contrary, the antioxidant levels in both liver and serum were decreased in carcinogen-administered animals, which was improved to normalcy upon morin administration. Cotreatment with morin prevented the elevation of marker enzymes induced by N-nitrosodiethylamine. The body weight of the animals decreased and their relative liver weight increased significantly on N-nitrosodiethylamine administration when compared to control group. However, cotreatment with morin significantly prevented the decrease of the body weight and increase in relative liver weight caused by DEN. Histological observations of liver tissue too correlated with the biochemical observations. In conclusion, these findings indicate that morin prevents lipid peroxidation, hepatic cell damage and protects the antioxidant system in N-nitrosodiethylamine-induced hepatocellular carcinogenesis. 相似文献