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1.
Camptothecin (CPT) and its analogues show potent antitumour activity. However, poor water solubility and severe side effects have restricted their applications in clinical practice. In this paper, a novel self‐assembly based on camptothecin and carbamoylmannose conjugates ( CPT‐Man ) was constructed. The self‐assembly increased the water solubility of camptothecin to 0.64 mg/ml and antitumour activity. Moreover, CPT‐Man could induce obvious cancer cell apoptosis. This work provides a new approach for exploring carbohydrate‐modified antitumour properties by self‐assembled CPT drugs.  相似文献   
2.
ABSTRACT

Introduction

We describe a new, third-generation of antibody-drug conjugates (ADCs) having a high drug payload against topoisomerase I, important for DNA function, and targeting selective tumor antigens, predominantly TROP-2.  相似文献   
3.
《药学学报(英文版)》2020,10(7):1294-1308
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.  相似文献   
4.
目的考察胆酸偶联喜树碱衍生物20(S)-O-甘氨酸-脱氧胆酸喜树碱(E2)、20(S)-O-醋酸-脱氧胆酸喜树碱(G2)在大鼠血浆和人工胃肠液中的稳定性。方法建立并优化高效液相色谱法,测定并比较E2、G2和喜树碱在大鼠血浆和人工胃肠液中的稳定性。结果在血浆和人工胃肠液中三者均有不同程度的减少,但E2、G2减少量均低于喜树碱。相对于人工胃肠液,三者在大鼠血浆中减少最为明显。三者在3种生物基质中发生了相似的降解,E2、G2主要发生水解生成喜树碱,而喜树碱则主要发生了内酯环开环。结论通过偶联胆酸合成得到的喜树碱衍生物在生物基质中具有明显高于喜树碱的稳定性,有助于维持喜树碱药效团内酯环的稳定。  相似文献   
5.
Cyclodextrins, cyclic oligomers of glucose, have been used in pharmaceutical formulations for decades as a result to their biocompatibilities, low toxicities and their abilities to solubilise organic small molecules via inclusion complex formation. The incorporation of cyclodextrins within polymers of numerous types, for use as drug delivery agents, has been explored. Illustrative of the flexibility in polymer chemistry and delivery application that is possible with these materials, two linear cyclodextrin-containing polymers are in preclinical and clinical development for the non-covalent delivery of nucleic acid therapeutics and covalent delivery of a small-molecule drug, respectively. This document provides an overview of the background and progress that has been made with these materials thus far, as well as suggestions for their future development and characterisation.  相似文献   
6.
Abstract

Camptothecin-20(s)-O-glycine ester-[N-(3′α, 12′α-dihydroxy-24′-carbonyl-5′β-cholan)] (A2), 10-(3′α,12′α-dihydroxy-5′β-cholan-24′-carboxyl)-(20?s)-camptothecin (C2), and 10-O-(3-O-(3′α, 12′α-dihydroxy-24′-carbonyl-5′β-cholan)-propyl)-(20S)-camptothecin (D2) are novel camptothecin-deoxycholic acid analogues. MTT assays were performed to assess the anticancer activity of these compounds against hepatocellular carcinoma SMMC-7721, breast carcinoma MCF-7, and colorectal carcinoma HCT-116 cells. A2 had a high killing ability on SMMC-7721 cells selectively, but C2 and D2 did not exhibit selectivity with regard to SMMC-7721 killing. Uptake assays were performed in an effort to elucidate the transport mechanisms of A2 into SMMC-7721 cells. A2 increased the mRNA expression of OATP1B3 (an organic anion-transporting polypeptide) and uptake of A2 was inhibited by rifampin (inhibitor of OATP1B3), which indicated that the transporter-mediated transport of A2 was mediated by OATP1B3. In addition, according to the western blot and apoptosis assays, we found that A2 killed SMMC-7721 cells by inducing cell apoptosis mainly via an AIF (apoptosis-inducing factor) pathway and a caspase-dependent mitochondria apoptosis pathway.  相似文献   
7.
目的 观察羟基喜树碱(hydroxy camptothecin,HCPT)联合放疗治疗晚期宫颈癌的近期疗效及不良反应.方法 37例Ⅲ期宫颈癌患者随机分为综合治疗组和单纯放疗组,行同期对比分析.综合治疗组在放疗的第一周和第四周每日放疗后加用HCPT 10 mg/d,每周连用5d.结果 放疗结束时综合治疗组总有效率较单纯放疗组高,差异有统计学意义(P<0.05).放疗后3个月,两组总有效率差异仍有统计学意义(P<0.05),不良反应差异无统计学意义(P>0.05).结论 HCPT联合放疗能提高晚期宫颈癌患者近期疗效,且不增加不良反应.  相似文献   
8.
Background: Camptothecin (CPT), a pentacyclic alkaloid isolated by Wall et al. in 1958 from the Chinese tree Camptotheca acuminata, was reported to possess an interesting antitumor activity. Late in 1985, it was reported by Liu et al. that the cytotoxic activity of CPT was attributed to a novel mechanism of action involving the nuclear enzyme classified as type I DNA topoisomerase. Since the explanation of the unique mechanism of action, many derivatives have been synthesized and some of them are in various stages of preclinical and clinical development. Among them, two derivatives, topotecan and irinotecan, have successfully entered into the market and are used as topoisomerase I poisons in clinical practice. Objective: The main focus of the present review is to describe the development of CPT derivatives over the years dividing them by decades according to the date of discovery and focusing attention on molecules that were published in patents. Results/conclusion: To summarize, > 150 patents have been deposited over the past 30 years. Structure–activity relationship studies suggest that substitutions at the 7-, 9- or 10-positions of most CPT derivatives enhance their antitumor activity, but at the 11- or 5-position usually lead to activity decrease.  相似文献   
9.
膀胱癌经膀胱灌注不同类型药物的治疗效果及安全性分析   总被引:1,自引:0,他引:1  
李可  万滨 《实用癌症杂志》2016,(9):1504-1506
目的 对膀胱癌患者经膀胱灌注不同类型的药物,观察其治疗效果,并分析其安全性.方法 将膀胱癌患者随机分为3组,分别对其经膀胱灌注丝裂霉素、吡柔比星、羟基喜树碱,随访比较其3个月、6个月、12个月、24个月复发率,比较其不良反应发生率.结果 丝裂霉素组3个月、6个月、12个月、24个月复发率明显高于吡柔比星组、羟基喜树碱组,差异有统计学意义(P<0.05);丝裂霉素组患者24个月有效率60%,明显低于吡柔比星组、羟基喜树碱组,差异有统计学意义(p<0.05).丝裂霉素组患者出现膀胱刺激征、血尿、血象异常、肝功能损害、肾功能损害、皮疹的发生率均明显高于吡柔比星组、羟基喜树碱组,差异有统计学意义(P<0.05);且吡柔比星组各项不良反应的发生率、总发生率均高于羟基喜树碱组,差异有统计学意义(P<0.05).结论 对膀胱癌患者进行膀胱灌注给药,选用吡柔比星、羟基喜树碱,均有较高疗效,但羟基喜树碱不良反应发生率低,耐受性好,安全有效.  相似文献   
10.
目的:观察去甲斑蝥素(norcantharidin,NCTD)能否缓解喜树碱(camptothecin,CPT)用药引起的骨髓抑制。方法:取Balb/c小鼠,采用概率单位法计算CPT半数致死量(median lethal dose,LD50)。以1 mg·kg-1作为CPT给药剂量,使用全血分析仪检测24 h内不同时间点白细胞浓度变化,为后续联合用药提供检测时间点参考。随后取Balb/c小鼠随机分为6组,分别为空白组,CPT(1 mg·kg-1)组,NCTD低、高剂量(10,20 mg·kg-1)组,CPT(1 mg·kg-1)+NCTD(10 mg·kg-1)组和CPT(1 mg·kg-1)+NCTD(20 mg·kg-1)组。连续灌胃2周,采用眼球采血法,应用全血分析仪检测进行相关指标的测定。流式细胞仪检测各组小鼠骨髓中性粒细胞的差异。病理组织切片评估肠道的毒性情况。结果:CPT LD50为1 mg·kg-1。CPT单独给药后6 h小鼠白细胞数目降至最少。24 h内与CPT单独用药比较,CPT+NCTD联合给药组白细胞、中性粒细胞数目明显上升(P0.05),嗜酸性粒细胞、嗜碱性粒细胞等无明显变化。连续灌胃2周,比较CPT单独用药,CPT+NCTD联合给药组白细胞数目明显上升(P0.05),其中淋巴细胞升高显著(P0.01),其他细胞无明显变化。流式细胞仪检测各组小鼠骨髓中性粒细胞的无明显差异,苏木素-伊红(HE)染色显示CPT主要毒靶器官小肠的病理变化短期、长期均不明显。结论:NCTD可减轻CPT用药引起的白细胞减少症,并没有增加其肠道毒性,为临床CPT应用,并减轻其毒性提供一定理论参考。  相似文献   
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