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排序方式: 共有157条查询结果,搜索用时 93 毫秒
1.
Cationic liposome-mediated delivery of siRNAs in adult mice   总被引:13,自引:0,他引:13  
RNA interference mediated by small interfering RNAs (siRNAs) is a powerful tool for dissecting gene function and drug target validation. siRNAs can be synthesized in large quantities and thus can be used to analyze a large number of sequences emerging from genome projects in a cost-effective manner. However, the major obstacle to the use of siRNAs as therapeutics is the difficulty involved in effective in vivo delivery. We used a fluorescein-labeled siRNA to investigate cationic liposome-mediated intravenous and intraperitoneal delivery in adult mice. We show that this simple approach can deliver siRNAs into various cell types. In addition, we show that in contrast to mouse cells, siRNAs can activate the non-specific pathway in human freshly isolated monocytes, resulting in TNF-alpha and IL-6 production. Taken together, the data provide a basis for lipid-mediated systemic delivery of siRNAs and indicate that certain siRNA sequences can activate the innate immunity response genes that can be beneficial for the treatment of cancer.  相似文献
2.
Heat shock proteins (HSPs) are recognized as significant participants in cancer immunity. We previously reported that HSP70 expression following hyperthermia using magnetic nanoparticles induces antitumor immunity. In the present study, we examine whether the antitumor immunity induced by hyperthermia is enhanced by administration of recombinant HSP70 protein into the tumor in situ. Hyperthermia was conducted using our original magnetite cationic liposomes (MCLs), which have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs and recombinant mouse HSP70 (rmHSP70) were injected into melanoma nodules in C57BL/6 mice, which were subjected to AMF for 30 min. Temperature within the tumor reached 43°C and was maintained by controlling the magnetic field intensity. The combined treatment strongly inhibited tumor growth over a 30-day period and complete regression of tumors was observed in 20% (2/10) of mice. It was also found that systemic antitumor immunity was induced in the cured mice. This study suggests that novel combined therapy using exogenous HSP70 and hyperthermia has great potential in cancer treatment.  相似文献
3.
The present study investigated the potency of the mannosylated cationic liposomes (Man liposomes) that we have developed in novel DNA vaccine carrier. Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA-encoding pDNA (pCMV-OVA) was constructed to evaluate DNA vaccination. The potency of the Man liposome/pCMV-OVA complex was compared with naked pCMV-OVA and that complexed with DC-Chol liposomes. In cultured mouse peritoneal macrophages, MHC class I-restricted antigen presentation of the Man liposome/pCMV-OVA complex was significantly higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes. After intravenous administration, OVA mRNA expression and MHC class I-restricted antigen presentation on CD11c+ cells and inflammatory cytokines, such as TNF-alpha, IL-12, and IFN-gamma, that can enhance the Th1 response of the Man liposome/pCMV-OVA complex were higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes. Also, the spleen cells from mice immunized by intravenous administration of the Man liposome/pCMV-OVA complex showed the highest proliferation response and IFN-gamma secretion. These findings suggest that the targeted delivery of DNA vaccine by Man liposomes is a potent vaccination method for DNA vaccine therapy.  相似文献
4.
Abstract: Under control conditions, superfused slices of the dorsal half of the lumbar enlargement from adult rats released Met-enkephalin-like material (MELM) that behaved as authentic Met-enkephalin under two different chromatographic procedures (Bio-gel filtration, HPLC). MELM release increased markedly on exposure of slices to batrachotoxin (0.5 μ M ) or to an excess of K+ (28 and 56 m M instead of 5.6 m M ). The K + -evoked release was totally dependent on the presence of Ca2+ in the super-fusing fluid whereas the spontaneous efflux of MELM was only partially Ca2+-dependent. Further experiments performed with tissues of polyarthritic rats indicated that the increase in their MELM levels was associated with a lower fractional rate constant of MELM release, therefore suggesting that spinal Met-enkephalin turnover might be reduced in chronically suffering animals. Examination of the possible modulation of MELM release by various neuroactive compounds present within the dorsal horn revealed that cholecystokinin (10 μ M ), but not its desulphated derivative, substance P-sulphoxide (10 μ M ), and to a lesser extent substance P, enhanced the K+-evoked MELM release. In contrast, γ-aminobutyric acid (10 μ M ) and (–)-baclofen (1 μ M ) partially prevented the stimulatory effect of K+ on MELM release. Other compounds such as serotonin, somatostatin, and neurotensin altered neither the spontaneous nor the K+-evoked release of MELM.  相似文献
5.
Cationic lipids enhance siRNA-mediated interferon response in mice   总被引:6,自引:0,他引:6  
RNA interference mediated by small interfering RNAs (siRNAs) shows promise as a powerful research tool for gene function studies. However, controversy exists over the potential of siRNA-induced interferon response in vitro and in vivo. In this study, we showed that although intravenous administration of siRNA alone is essentially inert, injection of siRNA complexed with cationic liposomes resulted in a potent induction of both type I and type II interferon responses. Furthermore, i.v. administration of cationic lipid/siRNA complexes led to activation of STAT1. This study suggests caution in data interpretation and the potential toxicity with in vivo use of siRNA, particularly when delivered via a cationic lipid vector. This study also suggests the potential of siRNA as an immunostimulatory agent for immunotherapy.  相似文献
6.
Zinc coupling potentiates anti-HIV-1 activity of baicalin   总被引:6,自引:0,他引:6  
Baicalin (BA) has been shown with anti-HIV-1 activity. Zinc is a nutrient element. The anti-HIV-1 activity of zinc complex of baicalin (BA-Zn) in vitro was studied and compared with the anti-HIV-1 activities between BA and BA-Zn in the present study. Our results suggested that BA-Zn has lower cytotoxicity and higher anti-HIV-1 activity compared with those of BA in vitro. The CC50s of BA-Zn and BA were 221.52 and 101.73 microM, respectively. The cytotoxicity of BA-Zn was about 1.2-fold lower than that of BA. The BA and BA-Zn inhibited HIV-1 induced syncytium formation, HIV-1 p24 antigen and HIV-1 RT production. The EC50s of BA-Zn on inhibiting HIV-1 induced syncytium formation (29.08 microM) and RT production (31.17 microM) were lower than those of BA (43.27 and 47.34 microM, respectively). BA-Zn was more effective than BA in inhibiting the activities of recombinant RT and HIV-1 entry into host cells. Zinc coupling enhanced the anti-HIV-1 activity of baicalin.  相似文献
7.
NO和茉莉酸甲酯对黄芩悬浮细胞生长及黄芩苷合成的影响   总被引:6,自引:0,他引:6  
以硝普钠(sodium nitroprusside,SNP)为一氧化氮(nitric oxide,NO)的供体,向黄芩(Scutellaria baicalensis)悬浮培养细胞系中添加SNP和茉莉酸甲酯(methyl jasmonate,MJ),考察这两种诱导子在不同的添加时间、添加浓度及混合配比使用对黄芩悬浮细胞系生长和黄芩苷含量的影响。研究结果表明:低浓度的外源NO有利于细胞的生长,但对黄芩苷积累无作用,而MJ有利于黄芩苷的合成,但抑制细胞生长,且两者的适用浓度范围和添加时间存在差异。在细胞培养初期(0天)添加0.05 mmol·L~(-1)SNP,而在细胞生长对数中期(8天)添加10μmol·L~(-1)的MJ,细胞鲜重可达到对照的1.2倍,黄芩苷总量达到对照的2.96倍。  相似文献
8.
Superfusion of slices from the dorsal half of the lumbar enlargement of rat spinal cord with Krebs-Henseleit medium supplemented with 30 microM bacitracin allowed the collection of substance P-like immunoreactive material (SPLI), which was released at a rate of approximately 10 pg/4 min. Tissue depolarization by an excess of K+ (30-60 mM) or veratridine (50 microM) induced a marked increase in SPLI outflow, provided that Ca2+ was present in the superfusing fluid. K+- or veratridine-induced SPLI overflow could be modulated in opposite directions by mu and delta opioid receptor agonists. Thus, the two preferential mu agonists Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO; 10 microM) and Tyr-D-Ala-Gly-MePhe-Met(O)5-OH (FK-33824; 0.1 microM) enhanced SPLI overflow from depolarized tissues, whereas the selective delta agonists Tyr-D-Thr-Gly-Phe-Leu-Thr (deltakephalin; 3 microM) and [2-D-penicillamine, 5-D-penicillamine]enkephalin (50 microM) reduced it. The effect of DAGO was antagonized by a low concentration (1 microM) of naloxone but not by the selective delta antagonist ICI-154129 (50 microM). In contrast, the latter drug prevented the inhibitory influence of delta agonists on K+-induced SPLI release. Complementary experiments with morphine (10 microM) and [2-D-alanine, 5-D-leucine]enkephalinamide (3 microM), in combination with 1 microM naloxone or 50 microM ICI-154129 for the selective blockade of mu or delta receptors, respectively, confirmed that the stimulation of mu receptors increased, whereas the stimulation of delta receptors reduced, SPLI overflow. The results suggest that, at the spinal level, and antinociceptive action of delta but not mu agonists might involve a presynaptic inhibition of substance P-containing primary afferent fibers.  相似文献
9.
A radioimmunoassay (RIA) was developed to measure fibroblast growth factor (FGF) using antiserum generated against a synthetic replicate of [Tyr10]FGF(1–10). The antisera, previously shown to be capable of inhibiting the biological action of FGF on bovine aortic arch endothelial cells in vitro [1], are highly specific for the amino-terminus of FGF. In the RIA, the antisera recognize the decapeptide antigen [Tyr10]FGF(1–10) and the intact mitogen on an equimolar basis and show less than 0.01% cross-reactivity with N-acetyl-[Tyr10]FGF(1–10).

Bovine adenohypophysial cells maintained in primary monolayer culture release and ir-FGF which is indistinguishable from the intact mitogen in as much as it is retained on heparin-Sepharose affinity columns and shows a dose-dependent and parallel displacement in RIA. The release of ir-FGF by the bovine adenohypophysis can be increased with forskolin (10−5 M) or KCl (50 mM). Preincubation of pituitary cells with 17β-estradiol has no measurable effects on basal ir-FGF, but increases the release after KCl treatment 2–3-fold. These results show that ir-FGF can be released by the bovine adenohypophysis in vitro and lend credence to the hypothesis that FGF plays a physiological role in the homeostatic mechanisms regulating mesoderm-derived cell growth.  相似文献

10.
电离辐射调控脂质体介导的CDglyTK基因杀伤人肝癌细胞   总被引:5,自引:0,他引:5  
利用EGR 1启动子、CDglyTK构建pcDNA3 EGR CDglyTK重组载体 ,以pcDNA3 CMV CDglyTK质粒为对照 ,经阳离子脂质体LipofectAMINE介导转染人肝癌 740 2细胞株 ,给予不同剂量 γ射线照射 ,通过Northern印迹、Western印迹分析 ,结果表明电离辐射可诱导转染pcDNA3 EGR CDglyTK肿瘤细胞中CDglyTK的表达 ,并呈剂量依赖性 ;而在pcDNA3 CMV CDglyTK实验组中无此诱导特性。转染pcDNA3 EGR CDglyTK的肿瘤细胞单独给予 8Gy的 γ 射线处理未见细胞明显死亡 ,而电离辐射与前药 [5 FC(fluorocytosine) GCV]的联合大大增强了杀伤肿瘤细胞的作用。研究结果证实EGR 1启动子具有电离辐射诱导特性 ,同时提示CMV启动子无此特性 ;5 FC与GCV的配伍有协同效应 ,电离辐射可明显增强肿瘤细胞对 5 FC、GCV的敏感性 ,其细胞毒性大于单独自杀基因或单独放疗。  相似文献
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