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101.
Chearwae W Anuchapreeda S Nandigama K Ambudkar SV Limtrakul P 《Biochemical pharmacology》2004,68(10):2043-2052
P-glycoprotein (Pgp, ABCB1) is an ATP-dependent drug efflux pump linked to development of multidrug resistance (MDR) in cancer cells. Previously [Biochem Pharmacol 2002;64:573-82], we reported that a curcumin mixture could modulate both function and expression of Pgp. This study focuses on the effect of three major curcuminoids--curcumin I, II and III purified from a curcumin mixture--on modulation of Pgp function in a multidrug resistant human cervical carcinoma cell line (KB-V1). The similar IC(50) values for cytotoxicity of curcuminoids of KB-V1, and KB-3-1 (parental drug sensitive cell line) suggest that these curcuminoids may not be substrates for Pgp. Treating the cells with non-toxic doses of curcuminoids increased their sensitivity to vinblastine only in the Pgp expressing drug resistant cell line, KB-V1, and curcumin I retained the drug in KB-V1 cells more effectively than curcumin II and III, respectively. Effects of each curcuminoid on rhodamine123, calcein-AM, and bodipy-FL-vinblastine accumulation confirmed these findings. Curcumin I, II and III increased the accumulation of fluorescent substrates in a dose-dependent manner, and at 15 microM, curcumin I was the most effective. The inhibitory effect in a concentration-dependent manner of curcuminoids on verapamil-stimulated ATPase activity and photoaffinity labeling of Pgp with the [(125)I]-iodoarylazidoprazosin offered additional support; curcumin I was the most potent modulator. Taken together, these results indicate that curcumin I is the most effective MDR modulator among curcuminoids, and may be used in combination with conventional chemotherapeutic drugs to reverse MDR in cancer cells. 相似文献
102.
Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration 总被引:6,自引:0,他引:6
Garcea G Jones DJ Singh R Dennison AR Farmer PB Sharma RA Steward WP Gescher AJ Berry DP 《British journal of cancer》2004,90(5):1011-1015
Studies in vitro and in animal models of colorectal and hepatocellular cancers suggest that curcumin is an effective chemopreventive agent. In this pilot trial, we investigated whether oral administration of curcumin results in concentrations of the agent in normal and malignant human liver tissue, which are sufficient to elicit pharmacological activity. In total, 12 patients with hepatic metastases from colorectal cancer received 450-3600 mg of curcumin daily, for 1 week prior to surgery. Levels of curcumin and its metabolites were measured by HPLC in portal and peripheral blood, bile and liver tissue. Curcumin was poorly available, following oral administration, with low nanomolar levels of the parent compound and its glucuronide and sulphate conjugates found in the peripheral or portal circulation. While curcumin was not found in liver tissue, trace levels of products of its metabolic reduction were detected. In patients who had received curcumin, levels of malondialdehyde-DNA (M(1)G) adduct, which reflect oxidative DNA changes, were not decreased in post-treatment normal and malignant liver tissue when compared to pretreatment samples. The results suggest that doses of curcumin required to furnish hepatic levels sufficient to exert pharmacological activity are probably not feasible in humans. 相似文献
103.
Odot J Albert P Carlier A Tarpin M Devy J Madoulet C 《International journal of cancer. Journal international du cancer》2004,111(3):381-387
Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is known to be an anti-oxidant and an anti-inflammatory agent. It has been demonstrated recently to possess anti-angiogenic effects and pro-apoptotic activities against Ehrlich ascites tumor cells. In the current study, curcumin was found to be cytotoxic in vitro for B16-R melanoma cells resistant to doxorubicin either cultivated as monolayers or grown in three-dimensional (3-D) cultures (spheroids). We have demonstrated that the cytotoxic effect observed in the 2 culture types can be related to the induction of programmed cell death. In our in vivo studies, we examined the effectiveness of a prophylactic immune preparation of soluble proteins from B16-R cells, or a treatment with curcumin as soon as tumoral appearance, alone or in combination, on the murine melanoma B16-R. The combination treatment resulted in substantial inhibition of growth of B16-R melanoma, whereas each treatment by itself showed little effect. Moreover, animals receiving the combination therapy exhibited an enhancement of their humoral anti-soluble B16-R protein immune response and a significant increase in their median survival time (> 82.8% vs. 48.6% and 45.7% respectively for the immunized group and the curcumin-treated group). Our study shows that curcumin may provide a valuable tool for the development of a therapeutic combination against the melanoma. 相似文献
104.
Alcohol is a neurotoxin associated with significant morbidity and mortality. Ethanol is found to induce a dose dependent increase in lipid peroxidation (LPO). The elevation in lipid peroxidative products and the loss of antioxidant defense potential are enhanced when alcohol is taken along with polyunsaturated fatty acid (PUFA) or heated PUFA. The present study was undertaken to evaluate the effects of curcumin and photo-irradiated curcumin on alcohol and PUFA induced LPO and lipid pro fi les in plasma. The levels of vitamin C and E were decreased significantly in alcohol + raw as well as heated PUFA groups. The treatment with curcumin and photo-irradiated curcumin (IC) increased their levels significantly. The increase was more significant in the IC group than the curcumin group. The levels of cholesterol, phospholipids (PL), triglycerides (TG), free fatty acids (FFA), thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP) were increased significantly in alcohol + raw as well as heated PUFA groups and the treatment with curcumin and IC, brought back the levels. But the IC reduced the levels more significantly than curcumin. Thus, our results indicate that IC is a more potent antioxidant than curcumin. 相似文献
105.
本文对姜黄药材中总姜黄素的提取纯化方法进行了较深入的实验研究,采用可见-紫外分光光度法测定提取物中总姜黄素的含量。并对超声辅助提取法做了考察,采用正交实验法对超声提取法提取工艺条件进行优选,得到最佳的提取工艺条件为:姜黄粉碎成40目,75%的乙醇超声提取,提取时间为60min.,姜黄素的提取得率为4.96%。 相似文献
106.
目的研究姜黄素对人肾癌786-O细胞体外生长及细胞周期的影响,为肾癌治疗提供理论依据。方法应用MTT比色法和流式细胞仪检测人肾癌786-O细胞增殖抑制率及细胞周期各时相的变化和凋亡率。结果姜黄素对人肾癌786-O细胞有抑制作用,存在剂量依赖(F=6207.813,P〈0.01)与时间依赖(F=1210.386,P〈0.01);流式细胞仪分析,G1期细胞增多,S期细胞减少,C2/M期细胞相对增多。结论姜黄素可以抑制人肾癌786-O细胞增殖,阻止G1期细胞向S期的进程,促进人肾癌786-O细胞凋亡。 相似文献
107.
Nidhi Bharal Agarwal Seema Jain Dheeraj Nagpal Nitin Kumar Agarwal Pramod K. Mediratta Krishna K. Sharma 《Fundamental & clinical pharmacology》2013,27(2):169-172
Contemporary research indicates promising anticonvulsant effect of curcumin. However, its poor oral bioavailability is a major hindrance toward its pharmacological action. Thus, this study was carried out to evaluate the acute effect of liposome‐entrapped curcumin on increasing current electroshock seizures (ICES) test, pentylenetetrazole (PTZ)‐induced seizures, and status epilepticus in mice. Liposome‐entrapped curcumin in doses 25 and 50 mg/kg demonstrated significant increase in seizure threshold current and latency to myoclonic and generalized seizures in ICES test and PTZ‐induced seizures, respectively. Similarly, liposomal‐entrapped curcumin also increased the latency to the onset and decreased the duration of seizures during status epilepticus in mice. To conclude, liposomal‐entrapped curcumin possesses anticonvulsant activity against status epilepticus in mice. 相似文献
108.
姜黄素是一种提取自姜黄的多酚类化合物,具有神经保护作用,可以通过血脑屏障,是治疗多种神经系统疾病候选的理想药物。在胶质瘤、脑血管病、癫痫、神经退行性疾病和创伤性脑损伤等神经系统疾病中的作用已受到广泛关注。然而,姜黄素因生物利用率低,导致应用受到限制。近年来,人们发现纳米颗粒可有效提高姜黄素生物利用率。众多前期临床试验中发现,纳米颗粒药物输送系统使姜黄素药理作用得到了良好的应用。因此,本文就姜黄素纳米颗粒对中枢神经系统各类疾病的作用及机制的最新研究进展进行综述,以期为姜黄素在神经系统的广泛应用提供参考。 相似文献
109.
姜黄素对胃癌细胞19300、1953、c-myc及乙酰化组蛋白H3和H4表达的影响 总被引:2,自引:0,他引:2
目的 了解姜黄素对胃癌细胞P300、P53、c-myc以及乙酰化组蛋白H3和H4表达的影响,探讨其抗胃癌的分子机制。方法 用不同浓度的姜黄素作用人胃腺癌细胞系SGC-7901,作用24、48h后,Rt-PCR法检测P300、P53、c-mycmRNA的表达;蛋白免疫印迹法检测乙酰化组蛋白H3、H4、P300、P53、c-myc蛋白的表达。结果 在胃癌细胞SGC-7901中P300和c-myc的表达随姜黄素浓度的改变而改变,在20μmol/L 24h时抑制作用较为明显,且两者具有相关性(r=0.976),而野生型p53则没有明显变化;姜黄素对乙酰化的组蛋白H3、H4都有抑制作用。也以20μmol/L 24h的作用最强。结论 姜黄素能抑制P300表达,进而抑制组蛋白H3和H4的乙酰化以及原癌基因c-myc的表达,但不影响抑癌基因P53的表达。提示姜黄素抑制组蛋白乙酰化酶P300可能是其抗癌的分子机制之-。 相似文献
110.
目的:研究姜黄素对雄激素非依赖性前列腺癌细胞株PC-3细胞体外作用及其对血管内皮生长因子(VEGF)表达的影响,探讨其抗肿瘤的作用机制。方法:分别用0、6.25、12.5、25、50μmol/L浓度的姜黄素作用于PC-3细胞,12、24、36、48、72、96h后台盼蓝拒染法、四甲基偶氮唑蓝(MTT)法检测细胞生长活性;24h后流式细胞仪测定细胞周期及凋亡的变化,透射电镜观察细胞超微结构变化;半定量RT-PCR法检测PC-3细胞内VEGF mRNA的表达;ELISA检测细胞上清液中VEGF浓度。结果:姜黄素能显著抑制PC-3细胞的增殖,呈剂量与时间依赖性,不同浓度姜黄素组之间及不同时间组之间差异均有统计学意义(P〈0.01)。不同浓度姜黄素诱导PC-3细胞出现剂量依赖性G2/M期阻滞(P〈0.01),且各浓度组凋亡细胞比例均显著高于空白对照组(P〈0.01),差异有统计学意义;姜黄素作用24h后PC-3细胞出现凋亡的形态学改变;PC-3细胞内VEGF mRNA的表达和细胞上清液中VEGF呈剂量依赖性降低。结论:姜黄素能显著抑制体外PC-3细胞的生长,并促进其G2/M期阻滞和凋亡,VEGF mRNA及蛋白的表达也明显降低,可能是其抑制肿瘤和血管生长的机制之一。 相似文献