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排序方式: 共有68条查询结果,搜索用时 31 毫秒
1.
Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine   总被引:55,自引:0,他引:55  
Wei YQ  Wang QR  Zhao X  Yang L  Tian L  Lu Y  Kang B  Lu CJ  Huang MJ  Lou YY  Xiao F  He QM  Shu JM  Xie XJ  Mao YQ  Lei S  Luo F  Zhou LQ  Liu CE  Zhou H  Jiang Y  Peng F  Yuan LP  Li Q  Wu Y  Liu JY 《Nature medicine》2000,6(10):1160-1166
The breaking of immune tolerance against autologous angiogenic endothelial cells should be a useful approach for cancer therapy. Here we show that immunotherapy of tumors using fixed xenogeneic whole endothelial cells as a vaccine was effective in affording protection from tumor growth, inducing regression of established tumors and prolonging survival of tumor-bearing mice. Furthermore, autoreactive immunity targeting to microvessels in solid tumors was induced and was probably responsible for the anti-tumor activity. These observations may provide a new vaccine strategy for cancer therapy through the induction of an autoimmune response against the tumor endothelium in a cross-reaction.  相似文献
2.
Joint immunization with two recombinant adenoviruses, one expressing hepatitis C virus (HCV) core and E1 proteins and another expressing IL-12 (RAdIL-12), strongly potentiates cellular immune response against HCV Ags in BALB/c mice when RAdIL-12 was used at doses of 1 x 105-1 x 107 plaque-forming units. However, cellular immunity against HCV Ags was abolished when higher doses (1 x 108 plaque-forming units) of RAdIL-12 were used. This immunosuppressive effect was associated with marked elevation of IFN-gamma and nitric oxide in the serum and increased cell apoptosis in the spleen. Administration of N-nitro-L -arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, to mice that received high doses of RAdIL-12 was lethal, whereas no apparent systemic toxicity by L -NAME was observed in those immunized with lower doses of the adenovirus. Interestingly, in mice immunized with recombinant adenovirus expressing core and E1 proteins of HCV in combination with RAdIL-12 at low doses (1 x 107 plaque-forming units), L -NAME inhibited T cell proliferation and CTL activity in response to HCV Ags and also production of Abs against adenoviral proteins. In conclusion, gene transfer of IL-12 can increase or abolish cell immunity against an Ag depending of the dose of the vector expressing the cytokine. IL-12 stimulates the synthesis of NO which is needed for the immunostimulating effects of IL-12, but apoptosis of T cells and immunosuppression ensues when IFN-gamma and NO are generated at very high concentrations.  相似文献
3.
S. Xie  *  X. Zhu  Y. Cui  *  R. J. Wootton    W. Lei  * Y. Yang  * 《Journal of Fish Biology》2001,58(4):999-1009
To investigate the nature of compenstory growth in fish, an 8 week study at 28°C was performed on juvenile gibel carp Carassius auratus gibelio weighing 6·6 g. Fish were starved for 0 (control), 1 (S1) or 2 (S2) weeks and then re-fed to satiation for 5 weeks. Weekly changes in weight gain, feed intake and body composition were monitored during re-feeding. No significant difference was found in final body weight between the three groups, indicating complete compensation in the deprived fish. The deprived groups caught up in body weight with that of the control after 2 weeks of re-feeding. Body fat: lean body mass ratio was restored to the control level within 1 week of re-feeding. In the re-feeding period, weekly gains in body weight, protein, lipid, ash and energy in the S1 group were significantly higher than in the controls for 1 week. For the S2 group, weekly gains in body weight, lipid, ash and energy were higher than in the controls for 2 weeks, and gain in protein was higher than in the controls for 3 weeks, though gain in body energy became elevated again during the last 2 weeks of the experiment. Feed intake remained higher than the control level for 3 weeks in the S1 group and 4 weeks in the S2 group. Growth efficiency was not significantly different among the three groups in any of the weeks during re-feeding. Compensatory responses in growth and especially feed intake tended to last longer than the recovery of body composition.  相似文献
4.
Selectins play a major role in the inflammatory reaction by initiating neutrophil attachment to activated vascular endothelium. Some heparin preparations can interact with L- and P-selectin; however, the determinants required for inhibiting selectin-mediated cell adhesion have not yet been characterized. We now report that carboxyl-reduced and sulfated heparin (prepared by chemical modifications of porcine intestinal mucosal heparin leading to the replacement of carboxylates by O-sulfate groups) and trestatin A sulfate (obtained by sulfation of trestatin A, a non-uronic pseudo-nonasaccharide extracted from Streptomyces dimorphogenes) exhibit strong anti-P-selectin and anti-L-selectin activity while lacking antithrombin-mediated anticoagulant activity. In vitro experiments revealed that both compounds inhibited P-selectin- and L-selectin-mediated cell adhesion under laminar flow conditions. Moreover, carboxyl-reduced and sulfated heparin and trestatin A sulfate were also active in vivo, as assessed by experiments showing 1) that microinfusion of trestatin A sulfate reduced by 96% leukocyte rolling along rat mesenteric postcapillary venules and 2) that both compounds inhibited (by 58-81%) neutrophil migration into thioglycollate-inflamed peritoneum of BALB/c mice. These results indicate that nonanticoagulant sulfated saccharides targeted at P-selectin and L-selectin may have therapeutic potential in inflammatory disorders.  相似文献
5.
A new vibrational imaging method based on coherent anti-Stokes Raman scattering (CARS) has been used for high-speed, selective imaging of neutral lipid droplets (LDs) in unstained live fibroblast cells. LDs have a high density of C-H bonds and show a high contrast in laser-scanning CARS images taken at 2,845 cm-1, the frequency for aliphatic C-H vibrations. The contrast from LDs was confirmed by comparing CARS and Oil Red O (ORO)-stained fluorescence images. The fluorescent labeling processes were examined with CARS microscopy. It was found that ORO staining of fixed cells caused aggregation of LDs, whereas fixing with formaldehyde or staining with Nile Red did not affect LDs. CARS microscopy was also used to monitor the 3T3-L1 cell differentiation process, revealing that there was an obvious clearance of LDs at the early stage of differentiation. After that, the cells started to differentiate and reaccumulate LDs in the cytoplasm in a largely unsynchronized manner. Differentiated cells formed small colonies surrounded by undifferentiated cells that were devoid of LDs. These observations demonstrate that CARS microscopy can follow dynamic changes in live cells with chemical selectivity and noninvasiveness. CARS microscopy, in tandem with other techniques, provides exciting possibilities for studying LD dynamics under physiological conditions without perturbation of cell functions.  相似文献
6.
Effect of relative meal size (0.6-24%) on specific dynamic action (SDA) was assessed in southern catfish juveniles (48.2+/-3.2 g) at 27.5 degrees C. Cutlets of freshly killed loach species were used as test diet. Energy expended during SDA was linearly correlated with relative meal size (r=0.949, p<0.001, N=47). There was no significant difference in SDA coefficient (energy expended on SDA quantified as a percentage of the energy content of the meal) among different relative meal size groups. Factorial metabolic scope increased from 1.47 to 4.08 when the relative meal size increased from 0.6% to 24%. The peak V O2 increased with meal size, but levelled when relative meal size gradually increased to the maximum. SDA duration showed a S-type (slow-fast-slow) increase course with increased meal size. The results of this study suggest that the high postprandial factorial metabolic scope and a trapezoid SDA curve might be the adaptation strategy of warm water sit-and-wait fish under the natural selection of evolution related to long-term food resources.  相似文献
7.
In previous growth experiments with carnivorous southern catfish (Silurus meridionalis), the non-fecal energy lose was positively related to dietary carbohydrate level. To test whether metabolic energy expenditure accounts for such energy loss, an experiment was performed with southern catfish juveniles (33.2-71.9 g) to study the effect of dietary carbohydrate level on fasting metabolic rate and specific dynamic action (SDA) at 27.5 degrees C. The fasting metabolic rate in this catfish was increased with dietary carbohydrate level, and the specific dynamic action (SDA) coefficient (energy expended on SDA as percent of assimilated energy) was not affected by dietary carbohydrate level. The results suggest that in southern catfish, carbohydrate overfeeding increases metabolic rate to oxidize unwanted assimilated carbohydrate. A discussion on the poor capacity of intermediate metabolism for adapting dietary carbohydrate in carnivorous fish and its possible relationship with facultative component of SDA was also documented in this paper.  相似文献
8.
An NAD(+)-dependent alcohol dehydrogenase was purified to homogeneity from Nocardia fusca AKU 2123. The enzyme catalyzed (S)-specific oxidation of 3-pentyn-2-ol (PYOH), i.e., part of the stereoinversion reaction for the production of (R)-PYOH, which is a valuable chiral building block for pharmaceuticals, from the racemate. The enzyme used a broad variety of secondary alcohols including alkyl alcohols, alkenyl alcohols, acetylenic alcohols, and aromatic alcohols as substrates. The oxidation was (S)-isomer specific in every case. The K(m) and Vmax for (S)-PYOH and (S)-2-hexanol oxidation were 1.6 mM and 53 mumol/min/mg, and 0.33 mM and 130 mumol/min/mg, respectively. The enzyme also catalyzed stereoselective reduction of carbonyl compounds. (S)-2-Hexanol and ethyl (R)-4-chloro-3-hydroxybutanoate in high optical purity were produced from 2-hexanone and ethyl 4-chloro-3-oxobutanoate by the purified enzyme, respectively. The K(m) and Vmax for 2-hexanone reduction were 2.5 mM and 260 mumol/min/mg. The enzyme has a relative molecular mass of 150,000 and consists of four identical subunits. The NH2-terminal amino acid sequence of the enzyme shows similarity with those of the carbonyl reductase from Rhodococcus erythropolis and phenylacetaldehyde reductase from Corynebacterium sp.  相似文献
9.
10.
视觉信号在中枢的整合:同步振荡产生的机理和功能   总被引:2,自引:0,他引:2  
神经系统内各信息通道的信号间如何整合?一个可能的途径就是通过同步振荡来协调。本文对同怕研究进展作了回顾,侧重介绍了视皮怪内同步振荡的提出、实验依据、产生的机理和功能意义,并对可能的进展作了展望。  相似文献
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