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排序方式: 共有106条查询结果,搜索用时 0 毫秒
81.
Sharada Labadie Peter S. Dragovich Kathy Barrett Wade S. Blair Philippe Bergeron Christine Chang Gauri Deshmukh Charles Eigenbrot Nico Ghilardi Paul Gibbons Christopher A. Hurley Adam Johnson Jane R. Kenny Pawan Bir Kohli Janusz J. Kulagowski Marya Liimatta Patrick J. Lupardus Rohan Mendonca Jeremy M. Murray Rebecca Pulk Mark Zak 《Bioorganic & medicinal chemistry letters》2012,22(24):7627-7633
Herein we describe our successful efforts in obtaining C-2 substituted imidazo-pyrrolopyridines with improved JAK1 selectivity relative to JAK2 by targeting an amino acid residue that differs between the two isoforms (JAK1: E966; JAK2: D939). Efforts to improve cellular potency by reducing the polarity of the inhibitors are also detailed. The X-ray crystal structure of a representative inhibitor in complex with the JAK1 enzyme is also disclosed. 相似文献
82.
Miloni A. Rathod Pamela M. Rogers Sharada D. Vangipuram Emily J. McAllister Nikhil V. Dhurandhar 《Obesity (Silver Spring, Md.)》2009,17(4):657-664
Several metabolic abnormalities are associated with relative excess or deficiency of adipose tissue. Identifying the regulators of adipogenic differentiation is critical for its successful manipulation. Ad36, a human adenovirus, is a novel factor that promotes adipogenesis. We exploited the adipogenic potential of Ad36 to reveal exogenous modifiers of adipogenesis in rodent preadipocyte cell line in the presence or absence of differentiation inducers methyl‐isobutyl‐xanthine, dexamethasone, and insulin (M, D, and I; MDI). A nonadipogenic human adenovirus Ad2 was used as a negative control for viral infection. First, we confirmed that, Ad36, but not Ad2, increases lipid accumulation in the presence or absence of MDI. Time‐course studies for expression of key genes of adipogenic cascade showed that it is Ad36, but not Ad2, which downregulated preadipocyte marker gene Wnt10b, and upregulated expression of early (C/EBPΔ and C/EBPβ), intermediate (PPARγ2), and late genes (aP2 and G3PDH) of adipogenic cascade even in the absence of MDI. In the presence of MDI, onset of expression of adipogenic genes coincided for Ad36 and control groups, but the expressions were significantly greater for the Ad36 group. Next, we observed that attenuation of Ad36 mRNA expression by an antiadenoviral agent reduced 3T3‐L1 differentiation, indicating that viral mRNA expression is required for the process. Furthermore, with or without MDI or its components, Ad36 significantly increased lipid accumulation in 3T3‐L1 cells. Cell confluency at the time of Ad36 infection positively influenced lipid accumulation. The results reveal that Ad36 is an MDI‐independent exogenous regulator of the adipogenic process. Elucidating the molecular pathways involved may reveal novel regulatory controls of adipogenesis. 相似文献
83.
Peter S. Dragovich Benjamin P. Fauber Laura B. Corson Charles Z. Ding Charles Eigenbrot HongXiu Ge Anthony M. Giannetti Thomas Hunsaker Sharada Labadie Yichin Liu Shiva Malek Borlan Pan David Peterson Keith Pitts Hans E. Purkey Steve Sideris Mark Ultsch Erica VanderPorten Xuying Zhang 《Bioorganic & medicinal chemistry letters》2013,23(11):3186-3194
A novel 2-thio-6-oxo-1,6-dihydropyrimidine-containing inhibitor of human lactate dehydrogenase (LDH) was identified by high-throughput screening (IC50 = 8.1 μM). Biochemical, surface plasmon resonance, and saturation transfer difference NMR experiments indicated that the compound specifically associated with human LDHA in a manner that required simultaneous binding of the NADH co-factor. Structural variation of the screening hit resulted in significant improvements in LDHA biochemical inhibition activity (best IC50 = 0.48 μM). A crystal structure of an optimized compound bound to human LDHA was obtained and explained many of the observed structure–activity relationships. 相似文献
84.
NADH oxidation. catalyzed by the microsomal enzyme system is stimulated on addition of polymeric vanitdate Maximum stimulation by polymeric vanadnte was obtained in the presence of phosphate buffer. The small stimulation obtained by metavanadat (500μM) increased on aciditication followed by neutralization. or on adding a trace amount of polymeric vanadate (1 μM). 相似文献
85.
Chandru H Sharada AC Bettadaiah BK Kumar CS Rangappa KS Sunila Jayashree K 《Bioorganic & medicinal chemistry》2007,15(24):7696-7703
In the present study, four novel dienone cyclopropoxy curcumin analogs 1a–4a were synthesized by nucleophillic substitution reaction with cyclopropyl bromide. The tumor inhibitory and anti-angiogenic effects of the synthetic compounds were studied on mouse Ehrlich ascites tumor (EAT) in vivo. The compounds 1a–4a increased the life span (% ILS) of EAT bearing mice with corresponding significant reduction in ascites volume and cell number and induced apoptotic bodies in EAT cells. Anti-angiogenic studies of the compounds demonstrated significant reduction of microvessel density (MVD) in the peritoneum wall sections of mice and induced avascular zone in CAM model. Our findings demonstrate that the tumor growth inhibitory effects of synthetic dienone cyclopropoxy curcumin analogs 1a–4a could be mediated by promoting apoptosis and inhibiting tumor angiogenesis. However, the compounds need to be explored further to assess its clinical relevance. 相似文献
86.
Sharada Gullapalli Vidya Shivaswamy T. Ramasarma C. K. Ramakrishna Kurup 《Molecular and cellular biochemistry》1989,90(2):155-164
Summary Mitochondria isolated from the livers of rats administered with sodium meta-, ortho-, or polyvanadate, but not vanadyl sulphate, exhibited enhanced Ca2+ — stimulated respiration and uptake of calcium. These effects were shown also by mitochondria isolated from livers perfused with polyvanadate. The concentration of acid-soluble calcium decreased significantly in the mitochondrial fraction on vanadate treatment, while that in the cytosol showed a corresponding increase. Phenoxybenzamine, an antagonist to a-adrenergic receptors, effectively inhibited vanadate-induced Ca2+ mobilization, but surgical sympathectomy was without effect. This is the first demonstration of vanadate mimicking -adrenergic agonists in vivo. 相似文献
87.
88.
Lead-induced increase in antioxidant enzymes and lipid peroxidation products in developing rat brain 总被引:6,自引:0,他引:6
Kiran Kumar Bokara Erika Brown Rashidi McCormick Prabhakara Rao Yallapragada Sharada Rajanna Rajanna Bettaiya 《Biometals》2008,21(1):9-16
Pregnant rats were treated with 0.4% lead acetate through drinking water from 6th day of gestation and this treatment was
continued till 21 post natal days (PND). Four regions of the brain namely hippocampus, cerebellum, frontal cortex and brain
stem were dissected at 10, 20, 30 and 40 PND for estimation of lipid peroxidation products (LPP), catalase (CAT) and superoxide
dismutase (SOD). The results indicate that there was a significant (P < 0.05) increase of LPP in exposed rats than their corresponding control at 10, 20 and 30 PND both in hippocampus and cerebellum.
At PND 40, the LPP of control and exposed were found to be almost same in both the tissues indicating recovery from lead toxicity.
CAT activity was significantly (P < 0.05) high in hippocampus of exposed rats up to PND 30 but up to PND 20 in cerebellum and frontal cortex. However, in brain
stem, a significant (P < 0.05) increase in CAT activity was observed only at PND 10. A significant (P < 0.05) increase in SOD activity was observed up to PND 30 both in hippocampus and cerebellum on lead exposure. Frontal cortex
exhibited a similar significant (P < 0.05) increase of SOD activity up to PND 20 and for brain stem up to PND 10. There was no significant change in the activity
of antioxidant enzymes (CAT and SOD) and LPP in all the four brain tissues of control and exposed rats at PND 40 indicating
recovery from lead-induced oxidative stress.
This research work was presented as a poster in Annual Biomedical Research Conference for Minority Students (ABRCMS) at Dallas,
Texas, USA, during November 10–13, 2004 and the abstract was printed on page 231 of the Conference Proceedings 相似文献
89.
Sharada Paudel Yeoun‐Hee Kim Man‐Il Huh Song‐Ja Kim Yongmin Chang Young Jeung Park Kyoo Won Lee Jae‐Chang Jung 《Journal of cellular biochemistry》2013,114(4):942-954
Here, we examined the role of ADAM10 during retinal cell differentiation in retinal sections and in vitro cultures of developing chick retinal cells from embryonic day 6 (ED6). Immunohistochemistry showed that ADAM10 is abundantly expressed in the inner zone of neuroblastic layer at ED5, and it becomes more highly expressed in the ganglion cell layer at ED7 and ED9. Western blotting confirmed that ADAM10 was expressed as an inactive pro‐form that was processed to a shorter, active form in control cultured cells, but in cultures treated with an ADAM10 inhibitor (GI254023X) and ADAM10‐specific siRNA, the level of mature ADAM10 decreased. Phase‐contrast microscopy showed that long neurite extensions were present in untreated cultures 24 h after plating, whereas cultures treated with GI254023X showed significant decreases in neurite extension. Immunofluorescence staining revealed that there were far fewer differentiated ganglion cells in ADAM10 siRNA and GI254023X‐treated cultures compared to controls, whereas the photoreceptor cells were unaltered. The Pax6 protein was more strongly detected in the differentiated ganglion cells of control cultures compared to ADAM10 siRNA and GI254023X‐treated cultures. N‐cadherin ectodomain shedding was apparent in control cultures after 24 h, when ganglion cell differentiation was observed, but ADAM10 siRNA and GI254023X treatment inhibited these processes. In contrast, N‐cadherin staining was strongly detected in photoreceptor cells regardless of ADAM10 siRNA and GI254023X treatment. Taken together, these data indicate that the inhibition of ADAM10 can inhibit Pax6 expression and N‐cadherin ectodomain shedding in retinal cells, possibly affecting neurite outgrowth and ganglion cell differentiation. J. Cell. Biochem. 114: 942–954, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
90.
Ronald Benjamin Atoshi Banerjee Sharada Ramaseri Sunder Sumanlatha Gaddam Vijaya Lakshmi Valluri Sharmistha Banerjee 《PloS one》2013,8(8)