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Kikuchi A Nieda M Schmidt C Koezuka Y Ishihara S Ishikawa Y Tadokoro K Durrant S Boyd A Juji T Nicol A 《British journal of cancer》2001,85(5):741-746
alpha-galactosylceramide (KRN 7000, alpha-GalCer) has shown potent in vivo anti-tumour activity in mice, including against melanoma and the highly specific effect of inducing proliferation and activation of human Valpha24+NKT-cells. We hypothesized that human Valpha24+NKT-cells activated by alpha-GalCer might exhibit anti-tumour activity against human melanoma. To investigate this, Valpha24+NKT-cells were generated from the peripheral blood of patients with melanoma after stimulation with alpha-GalCer pulsed monocyte-derived dendritic cells (Mo-DCs). Valpha24+NKT-cells did not exhibit cytolytic activity against the primary autologous or allogeneic melanoma cell lines tested. However, proliferation of the melanoma cell lines was markedly suppressed by co-culture with activated Valpha24+NKT-cells (mean +/- SD inhibition of proliferation 63.9 +/- 1.3%). Culture supernatants of activated Valpha24+NKT-cell cultures stimulated with alpha-GalCer pulsed Mo-DCs exhibited similar antiproliferative activities against melanoma cells, indicating that the majority of the inhibitory effects were due to soluble mediators rather than direct cell-to-cell interactions. This effect was predominantly due to release of IFN-gamma, and to a lesser extent IL-12. Other cytokines, including IL-4 and IL-10, were released but these cytokines had less antiproliferative effects. These in vitro results show that Valpha24+NKT-cells stimulated by alpha-GalCer-pulsed Mo-DCs have anti-tumour activities against human melanoma through antiproliferative effects exerted by soluble mediators rather than cytolytic effects as observed against some other tumours. Induction of local cytokine release by activated Valpha24+NKT-cells may contribute to clinical anti-tumour effects of alpha-GalCer. 相似文献
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D-氨基葡萄糖盐酸盐体外抗肿瘤及其免疫调节作用 总被引:4,自引:1,他引:3
目的研究D-氨基葡萄糖盐酸盐(GAH)体外抗肿瘤作用和免疫增强作用。方法MTT法观察体外GAH对肿瘤细胞生长和小鼠淋巴细胞增殖的影响,酶联免疫法(ELISA)观察GAH对淋巴细胞分泌细胞因子IL-2的影响。结果GAH明显抑制SGC-7901细胞的生长,对HepG-2、LS-174细胞生长的抑制作用较弱。GAH具有有丝分裂原样的作用,能够诱导淋巴细胞增殖并且分泌IL-2。结论GAH有一定的抗肿瘤作用和免疫增强作用。 相似文献
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扇贝裙边糖胺聚糖抗肿瘤作用和对荷瘤小鼠免疫功能的影响 总被引:3,自引:0,他引:3
目的:研究扇贝裙边糖胺聚糖(SS-GAG)的抗癌作用及对荷瘤小鼠免疫功能的影响。方法:建立小鼠移植性S180实体瘤模型,观察SS-GAG的抑瘤率以及对荷瘤小鼠的体质量、肝质量、白细胞计数、脾指数、胸腺指数的影响,同时观察SS-GAG对荷瘤小鼠细胞免疫活性的影响。结果:SS-GAG可明显抑制S180实体瘤的生长,SS-GAG与环磷酰胺联用可使化疗药物的抗癌作用增强并能有效提升减少的白细胞;能显著增强荷瘤小鼠腹腔巨噬细胞的吞噬能力和杀伤活性,增强荷瘤小鼠脾淋巴细胞的转化增殖和NK细胞活性。结论:SS-GAG可显著抑制肿瘤生长,与环磷酰胺联用时有减毒增效作用;并能增强荷瘤小鼠的免疫功能。 相似文献
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Cell expansion and metastasis are considered hallmarks of tumour progression. Therefore, efforts have been made to develop novel anti-cancer drugs that inhibit both the proliferation and the motility of tumour cells. Synthetic alkylphospholipids, compounds with aliphatic side chains that are ether linked to a glycerol backbone, are structurally derived from platelet-activating factor and represent a new class of drugs with anti-proliferative properties in tumour cells. These compounds do not interfere with the DNA or mitotic spindle apparatus of the cell. Instead, they are incorporated into cell membranes, where they accumulate and interfere with lipid metabolism and lipid-dependent signalling pathways. Recently, it has been shown that the most commonly studied alkylphospholipids inhibit proliferation by inducing apoptosis in malignant cells while leaving normal cells unaffected. This review focuses on a novel group of synthetic alkylphospholipids, the glycosidated phospholipids, which contain carbohydrates or carbohydrate-related molecules at the sn-2 position of the glycerol backbone. Members of this subfamily also exhibit anti-proliferative capacity and modulate the cell adhesion, differentiation, and migration of tumour cells. Among this group, Ino-C2-PAF shows the highest efficacy and low cytotoxicity. Apart from its anti-proliferative effect, Ino-C2-PAF strongly reduces cell motility via its inhibitory effect on the phosphorylation of the cytosolic tyrosine kinases FAK and Src. Signalling pathways under the control of the FAK/Src complex are normally required for both migration and proliferation and play a prominent role in tumour progression. We intend to highlight the potential of glycosidated phospholipids, especially Ino-C2-PAF, as a promising new group of drugs for the treatment of hyperproliferative and migration-based skin diseases. 相似文献
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Holthuis JJ Römkens FM Pinedo HM van Oort WJ 《Journal of pharmaceutical and biomedical analysis》1983,1(1):89-97
A sensitive high-performance liquid chromatographic (HPLC) assay of the antineoplastic agent VP 16-213 (etoposide) in plasma is described. The system discriminates between the parent compound and possible metabolites, including the aglycone and the cis isomer. After extraction with 1,2-dichloroethane the drugs are chromatographed on a reversed-phase phenyl column with amperometric detection. Quantitative response is linear up to 250 ng/ml for 1 ml human plasma and up to 40.0 mug/ml for 0.1 ml human plasma. The detection limit is ca 2 ng/ml in plasma. Preliminary pharmacokinetic results show that the sensitivity and selectivity of the assay are adequate to establish plasma concentrations over 8-12 half-lives during elimination of the drug. 相似文献
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In this study, the anti-tumour activity of selenium-protein polysaccharide (SPP), a water extract of the rich selenium Agaricus blazei, was tested both in vivo and in vitro. The results of in vivo experiments show that SPP at doses of 50 and 100 mg/kg inhibits proliferation of implanted Sarcoma 180 by 22 and 37.69%, respectively, and promotes lymphocyte transformation and natural killer (NK) cells activity in tumour bearing mice. During the in vitro experiment, we treated the tumour and non-tumour bearing mice with SPP, and prepared serum treated with SPP (SerumSPP). The results show that SerumSPP, whether from tumour or non-tumour bearing mice, significantly inhibits K562 cells proliferation and induces their apoptosis, and also significantly increases caspase-3 activity of K562 cells. However, the difference in anti-tumour activity of SerumSPP between tumour and non-tumour bearing mice is significantly different (p<0.01). The results, according to the studies both in vivo and in vitro, imply that SPP extracted from rich selenium A. blazei can inhibit growth of implanted Sarcoma 180 and promote lymphocyte transformation and NK cells activity in vivo. Additionally, SerumSPP can inhibit proliferation and cause apoptotic morphological changes and the fragmentation of internucleosomal DNA, and increase caspase-3 activity of K562 cells in vitro, which indicates that apoptosis of K562 cells induced by SerumSPP may be related to up-regulation of caspase-3. 相似文献
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Jiayu Chen Jiaqi Chen Xintai Wang Chibo Liu 《African journal of traditional, complementary, and alternative medicines》2014,11(1):15-22