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21.
The benzodiazepine antagonist properties of Ro 15-1788 were evaluated in rats trained to discriminate between saline and either 1.0 mg/kg of diazepam or 10 mg/kg of pentobarbital in a two-choice discrete-trial shock avoidance procedure. When administered alone, 1.0 mg/kg of diazepam and 10 mg/kg of pentobarbital produced comparable amounts of drug-appropriate responding (> 84%), whether rats were trained to discriminate between diazepam or pentobarbital and saline. Ro 15-1788 (3–32 mg/kg, p.o.), administered 10 min before diazepam or pentobarbital, produced a dose-related blockade of the discriminative effects of diazepam in both groups of rats, but was completely ineffective in blocking the discriminative effects of pentobarbital. The dose-effect curve for the discriminative effects of diazepam was shifted to the right in a parallel fashion 3- and 13-fold by 10 and 32 mg/kg of Ro 15-1788, respectively, indicating that Ro 15-1788 acts as a surmountable, competitive antagonist of diazepam. When administered alone, Ro 15-1788 (32–100 mg/kg, p.o.) produced primarily saline-appropriate responding, although 100 mg/kg of Ro 15-1788 produced drug-appropriate responding in one out of eight rats. When administered orally 30 min after diazepam, Ro 15-1788 (32 mg/kg) completely reversed within 10 min the discriminative effects of diazepam. The blockade of diazepam's discriminative effects by 32 mg/kg of Ro 15-1788 appeared to last at least as long (approximately 2 hr) as the effects of diazepam alone. 相似文献
22.
BOENA ARSKA-MACIEJEWSKA IRENA SISKA EWA WITKOWSKA STANISAW LEWAK 《Physiologia plantarum》1980,48(4):532-535
The activity of acid lipase and the level of gibberellin A4 (GA4) were determined in apple embryos excised from seeds after different time periods of stratification and subsequently cultured in darkness at 4°C or at 25°C. Enzyme activity and GA4 content were higher at 4°C. Exogenous gibberellin stimulated lipase activity, while AMO-1618, an inhibitor of gibberellin biosynthesis, inhibited, to the same degree, both the enzyme activity and the GA4 accumulation. The involvement of GA4 and lipolytic enzymes in cold-mediated removal of embryonal dormancy has been discussed and compared with the role of these two factors in light-stimulated germination of dormant apple embryos, described earlier (Smoleńska and Lewak 1974). 相似文献
23.
24.
Margot C. Herling Clement F. Cupido Patrick J. O'Farrell Lozelle Du Plessis 《Restoration Ecology》2009,17(6):827-836
Nonsustainable ostrich farming practices have degraded large areas of the Little Karoo, a semiarid region in South Africa. The Little Karoo lies within the Succulent Karoo biome, a recognized biodiversity hotspot. A financial feasibility analysis was undertaken from a private landowner’s perspective to examine the costs and benefits of rehabilitating degraded areas thereby allowing farmers to shift their production focus from ostrich to sheep farming, a financially stable and relatively conservation‐compatible land use. Our aim was to raise awareness, at a private landowner level, to the opportunity costs incurred through unsustainable land use practices. We calculated and contrasted net present values for rehabilitation and no rehabilitation scenarios and investigated model sensitivities relating to seed costs, seedling survival and ostrich product prices. Rehabilitation was not found to be financially feasible for private landholders over 20 years. Seedling survival and associated seed costs were found to have strong controlling effects. Third parties need to contribute both financially and in terms of research outputs if sustainable land use practices are to be achieved in this area. This study elucidates the true costs associated with the unsustainable practice of ostrich farming and sounds a cautionary warning. 相似文献
25.
Lotte M Kruidenier Saskia PA Nicolaï Edith M Willigendael Rob A de Bie Martin H Prins Joep AW Teijink 《BMC cardiovascular disorders》2009,9(1):1-7
Background
Pharmacological inhibition of endothelial arginase-II has been shown to improve endothelial nitric oxide synthase (eNOS) function and reduce atherogenesis in animal models. We investigated whether the endothelial arginase II is involved in inflammatory responses in endothelial cells.Methods
Human endothelial cells were isolated from umbilical veins and stimulated with TNFα (10 ng/ml) for 4 hours. Endothelial expression of the inflammatory molecules i.e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were assessed by immunoblotting.Results
The induction of the expression of endothelial VCAM-1, ICAM-1 and E-selectin by TNFα was concentration-dependently reduced by incubation of the endothelial cells with the arginase inhibitor L-norvaline. However, inhibition of arginase by another arginase inhibitor S-(2-boronoethyl)-L-cysteine (BEC) had no effects. To confirm the role of arginase-II (the prominent isoform expressed in HUVECs) in the inflammatory responses, adenoviral mediated siRNA silencing of arginase-II knocked down the arginase II protein level, but did not inhibit the up-regulation of the adhesion molecules. Moreover, the inhibitory effect of L-norvaline was not reversed by the NOS inhibitor L-NAME and L-norvaline did not interfere with TNFα-induced activation of NF-κB, JNK, p38mapk, while it inhibited p70s6k (S6K1) activity. Silencing S6K1 prevented up-regulation of E-selectin, but not that of VCAM-1 or ICAM-1 induced by TNFα.Conclusion
The arginase inhibitor L-norvaline exhibits anti-inflammatory effects independently of inhibition of arginase in human endothelial cells. The anti-inflammatory properties of L-norvaline are partially attributable to its ability to inhibit S6K1. 相似文献26.
Jane E Girling Jacqueline F Donoghue Fiona L Lederman Leonie M Cann Marc G Achen Steven A Stacker Peter AW Rogers 《Reproductive biology and endocrinology : RB&E》2010,8(1):84
Background
It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. 相似文献27.
Kop EN Adriaansen J Smeets TJ Vervoordeldonk MJ van Lier RA Hamann J Tak PP 《Arthritis research & therapy》2006,8(5):R155-11
Synovial tissue of rheumatoid arthritis (RA) patients is characterised by an influx and retention of CD97-positive inflammatory
cells. The ligands of CD97, CD55, chondroitin sulfate B, and α5β1 (very late antigen [VLA]-5) are expressed abundantly in
the synovial tissue predominantly on fibroblast-like synoviocytes, endothelium, and extracellular matrix. Based upon this
expression pattern, we hypothesise CD97 expression to result in accumulation of inflammatory cells in the synovial tissue
of RA patients. To determine the therapeutic effect of blocking CD97 in an animal model of RA, collagen-induced arthritis
was induced in a total of 124 DBA/J1 mice. Treatment was started on day 21 (early disease) or on day 35 (longstanding disease)
with the blocking hamster anti-mouse CD97 monoclonal antibody (mAb) 1B2, control hamster immunoglobulin, or NaCl, applied
intraperitoneally three times a week. The paws were evaluated for clinical signs of arthritis and, in addition, examined by
radiological and histological analysis. Mice receiving 0.5 mg CD97 mAb starting from day 21 had significantly less arthritis
activity and hind paw swelling. Furthermore, joint damage and inflammation were reduced and granulocyte infiltration was decreased.
When treatment was started on day 35, CD97 mAb treatment had similar effects, albeit less pronounced. The results support
the notion that CD97 contributes to synovial inflammation and joint destruction in arthritis. 相似文献
28.
TAXONOMY OF ALBIAN GAVELINELLIDAE (FORAMINIFERA) FROM THE LOWER SAXONY BASIN, GERMANY 总被引:2,自引:0,他引:2
JAROSAW TYSZKA 《Palaeontology》2006,49(6):1303-1334
29.
Alexandra Miranville Andreas W. Herling Gabriele Biemer‐Daub Marc D. Voss 《Obesity (Silver Spring, Md.)》2010,18(12):2247-2254
Macrophage infiltration into adipose tissue (AT‐MP) is thought to induce insulin resistance and diabetes in obesity. Here, we investigated the effect of the antiobesity drug SR141716 (a CB1 antagonist) on macrophage‐mediated inhibition of insulin signaling in adipocytes. THP1 macrophages (THP1) were stimulated in vitro with lipopolysaccharide (LPS) and SR141716 or vehicle. The resulting conditioned medium (CM) was analyzed and incubated on human adipocytes. CM from LPS‐stimulated THP1 inhibited insulin‐induced AKT phosphorylation in adipocytes, in contrast to CM from nonactivated THP1. Moreover, it contained higher concentrations of tumor necrosis factor‐α (TNFα) and lower levels of the anti‐inflammatory cytokine IL‐10. SR141716 reduced TNFα production and increased IL‐10 secretion, resulting in a rescue of insulin signaling in adipocytes. To confirm these findings in vivo, AT‐MP CM from cafeteria diet‐fed or Zucker diabetic fatty (ZDF) rats that had received SR141716 for 3 weeks were isolated, analyzed, and incubated with adipocytes. Cafeteria diet induced macrophage‐mediated inhibition of insulin signaling in adipocytes. Interestingly, SR141716 rescued insulin‐induced glucose uptake in adipocytes. Finally, AT‐MP CM from obese ZDF rats inhibited insulin‐stimulated glucose uptake in adipocytes in contrast to AT‐MP CM from lean ZDF rats. After treatment with SR141716, AT‐MP CM rescued insulin‐induced glucose uptake in adipocytes. In summary, our data indicate that CB1 receptor antagonism in macrophages modified their cytokine production and improved the insulin responsiveness of adipocytes that had been incubated with macrophage CM. Thus, SR141716 ameliorated adipose tissue insulin resistance by direct action on AT‐MP demonstrating a novel peripheral mode of action of CB1 antagonism. 相似文献
30.
Lucas A Smolders Bj?rn P Meij David Onis Frank M Riemers Niklas Bergknut Richard Wubbolts Guy CM Grinwis Martin Houweling Marian JA Groot Koerkamp Dik van Leenen Frank CP Holstege Herman AW Hazewinkel Laura B Creemers Louis C Penning Marianna A Tryfonidou 《Arthritis research & therapy》2013,15(1):R23