全文获取类型
收费全文 | 567篇 |
免费 | 18篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 4篇 |
妇产科学 | 3篇 |
基础医学 | 22篇 |
口腔科学 | 9篇 |
临床医学 | 4篇 |
内科学 | 11篇 |
神经病学 | 2篇 |
特种医学 | 5篇 |
外科学 | 3篇 |
综合类 | 34篇 |
预防医学 | 97篇 |
药学 | 348篇 |
1篇 | |
中国医学 | 28篇 |
肿瘤学 | 24篇 |
出版年
2024年 | 1篇 |
2022年 | 6篇 |
2021年 | 8篇 |
2020年 | 9篇 |
2019年 | 7篇 |
2018年 | 13篇 |
2017年 | 30篇 |
2016年 | 21篇 |
2015年 | 15篇 |
2014年 | 45篇 |
2013年 | 59篇 |
2012年 | 39篇 |
2011年 | 44篇 |
2010年 | 38篇 |
2009年 | 36篇 |
2008年 | 49篇 |
2007年 | 38篇 |
2006年 | 17篇 |
2005年 | 15篇 |
2004年 | 19篇 |
2003年 | 17篇 |
2002年 | 4篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 8篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 1篇 |
排序方式: 共有595条查询结果,搜索用时 15 毫秒
531.
François Richeux Marta Cascante Rachid Ennamany Dominique Saboureau Edmond Ekué Creppy 《Archives of toxicology》1999,73(7):403-409
Capsaicin, a natural product of Capsicum species, induces excitation of pain perception at nociceptive terminals. Our previous studies have shown that capsaicin inhibits
protein synthesis in cultured monkey kidneys cells (Vero cells) and in primoculture of rat astrocytes. We have now investigated
the effect of capsaicin on human neuroblastoma cells SHSY-5Y. The cytotoxicity has been assessed by incorporation of [3H]L-leucine into cellular protein in the presence of capsaicin and the genotoxicity has been evaluated using the comet assay
and the fragmentation assay after incubation of neuroblastoma cells with 25–100 μM capsaicin. The concentration required to
inhibit 50% of the protein synthesis (IC50) was found to be 60 μM after incubation with the toxin during one cellular cycle (5 days) of SHSY-5Y. The results of the
comet test and DNA fragmentation assay clearly suggest that capsaicin is able to induce DNA strand breaks already with concentrations
in the range of 50 μM, corresponding to 29.3 μM of capsaicin not bound to alpha-1 acid glycoprotein. Several daily topical
applications of preparations containing 0.075% of capsaicin could lead to blood capsaicin concentration of this order of magnitude
following transdermal passage (5% of the total quantity applied). Because DNA strand breaks or DNA lesions may affect cellular
functions, lead to cell death and/or mutagenesis, our data in case of inappropriate DNA repair may have important implications
for the possible health threats of capsaicin, specially in the case of misuse of capsaicin preparations in pathological situations.
Received: 30 November 1998 / Accepted: 16 June 1999 相似文献
532.
Gerrit J.A. Speijers Louis H.T. Dederen Hiskias Keizer 《Regulatory toxicology and pharmacology : RTP》2009
In this paper a sub-chronic (13 weeks) toxicity study in rats and an in vitro genotoxicity study with Korean pine (Pinus koraiensis Siebold & Zucc.) nut oil, KPNO (PinnoThin™) are described. Both studies were performed in compliance with GLP, and in line with OECD guidelines applicable. 相似文献
533.
William L Stone Koyamangalath Krishnan Sharon E Campbell Victoria E Palau 《World journal of gastrointestinal oncology》2014,6(3):55-66
This review focuses on the roles antioxidants and pro-oxidants in colorectal cancer (CRC). Considerable evidence suggests that environmental factors play key roles in the incidence of sporadic CRC. If pro-oxidant factors play an etiological role in CRC it is reasonable to expect causal interconnections between the well-characterized risk factors for CRC, oxidative stress and genotoxicity. Cigarette smoking, a high dietary consumption of n-6 polyunsaturated fatty acids and alcohol intake are all associated with increased CRC risk. These risk factors are all pro-oxidant stressors and their connections to oxidative stress, the intestinal microbiome, intestinal microfold cells, cyclooxygenase-2 and CRC are detailed in this review. While a strong case can be made for pro-oxidant stressors in causing CRC, the role of food antioxidants in preventing CRC is less certain. It is clear that not every micronutrient with antioxidant activity can prevent CRC. It is plausible, however, that the optimal food antioxidants for preventing CRC have not yet been critically evaluated. Increasing evidence suggests that RRR-gamma-tocopherol (the primary dietary form of vitamin E) or other “non-alpha-tocopherol” forms of vitamin E (e.g., tocotrienols) might be effective. Aspirin is an antioxidant and its consumption is linked to a decreased risk of CRC. 相似文献
534.
目的研究槲皮素对体外哺乳动物的细胞遗传毒性。方法采用80、40、20、10、5 mg/L5个剂量组的槲皮素在有或无代谢活化条件下处理体外培养的中国地鼠肺成纤维细胞(CHL)3 h后更换新鲜培养液,恢复生长21 h后收获细胞制片,观察槲皮素对哺乳动物细胞染色体的影响。采用200、100、50、25和12.5 mg/L 5个剂量组的槲皮素在有或无代谢活化条件下处理中国仓鼠肺成纤维细胞(V79)3 h后,经过7 d的次黄嘌呤鸟嘌呤磷酸核糖转移酶(HGPRT)突变基因表达和7 d突变基因选择后计数集落形成率并计突变频率,观察槲皮素对哺乳动物HGPRT基因位点的影响。结果在有或无代谢活化条件下槲皮素在浓度〉10 mg/L均能够诱导CHL细胞染色体断裂和交换等,染色体细胞畸变率显著增加(P〈0.01);而在有或无代谢活化与溶剂对照组相比较槲皮素各剂量组均未发生基因突变频率显著增加(P〉0.05)。结论在体外试验条件下,槲皮素对哺乳动物细胞显示出明显致突变性,存在潜在的遗传毒性。 相似文献
535.
目的 对一种以二甲基硅油、甘油、羧甲基纤维素钠为成分的肠镜润滑消泡剂进行细胞毒性和遗传毒性评价,为这种肠镜润滑消泡剂在临床使用提供生物安全依据。方法 选择琼脂扩散试验对肠镜润滑消泡剂进行体外细胞毒性检测,选择细菌回复突变试验(Ames试验)、用小鼠淋巴瘤细胞进行的体外哺乳动物细胞基因突变试验(MLA试验)、体外哺乳动物细胞染色体畸变试验进行遗传毒性检测。细胞毒试验,将样品放置在固化的琼脂层上与L929细胞间接接触24 h,用中性红对细胞进行染色后显微镜下观察细胞毒性。Ames试验选用TA97a、TA98、TA100、TA102、TA1535五种组氨酸缺陷型鼠伤寒沙门氏菌株,观察肠镜润滑消泡剂对细菌回复突变率的影响;MLA试验采用小鼠淋巴瘤细胞与样品溶液接触3 h和24 h,通过计算其平板效率和大小集落形成数目计算突变频率,判断受试样品对小鼠淋巴瘤细胞突变率的影响;体外哺乳动物细胞染色体畸变试验,使样品溶液与中华地鼠肺细胞(CHL细胞)接触6 h和24 h,通过对处于有丝分裂中期的CHL细胞的染色体畸变情况进行分析,评价肠镜润滑消泡剂对CHL细胞潜在的致突变性。结果 在细胞毒试验中,受试样品与阴性对照相比,细胞数量相对较少且受试样品显微镜下观察有少量畸形和退化的细胞,为轻微的细胞毒性;Ames试验样品组回变菌落数均未比阴性对照回变菌落数增加1倍或者1倍以上且无重复性;MLA试验样品组MF值与阴性对照相比无超过126×10-6的增长;染色体畸变试验受试样品组染色体结构畸变率与阴性对照相比,差异无统计学意义(P>0.05)。结论 以二甲基硅油、甘油、羧甲基纤维素钠为成分的肠镜润滑消泡剂无潜在的细胞毒性和遗传毒性,可进一步用于临床研究。 相似文献
536.
Tamura T Mitsumori K Totsuka Y Wakabayashi K Kido R Kasai H Nasu M Hirose M 《Toxicology》2006,222(3):213-224
To clarify the in vivo genotoxic potential of kojic acid (KA), formation of DNA adducts and 8-hydroxy-deoxyguanosine (8-OHdG) in the thyroids of male rats subjected to dietary administration of 2% KA for 2 weeks were assessed by 32P-postlabeling analysis and with a high-performance liquid chromatography system coupled to an electrochemical detector (ECD), respectively. In addition, to investigate possible tumor initiation activity, male F344 rats were given diet containing 0, 0.02, 0.2 or 2% kojic acid for 8 weeks followed by administration of 0.1% sulfadimethoxine (SDM), a thyroid tumor promoter, in the drinking water for 23 weeks with a subsequent 13-week recovery period (two-stage thyroid tumorigenesis model). Rats given four times by s.c. injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN; 700 mg/kg bw) during the initiation period followed by administration of 0.1% SDM and rats given diet containing 2% KA for the initial 8 weeks or for the entire 31 weeks of the experiment, or basal diet alone were provided as controls. DNA adducts were not formed, and the 8-OHdG level was not increased in the thyroids of rats given 2% KA for 2 weeks. In the two-stage thyroid tumorigenesis model, neither adenomas nor carcinomas were induced in the groups given 0, 0.02, 0.2 or 2% KA followed by 0.1% SDM administration, and incidences and multiplicities of focal follicular cell hyperplasias did not demonstrate any significant intergroup differences at the end of administration and recovery periods. In contrast, incidences and multiplicities of focal follicular cell hyperplasias, adenomas and carcinomas were all significantly increased in the DHPN + 0.1% SDM group. Although the incidences and multiplicities of focal follicular cell hyperplasias in the group given 2% KA for 31 weeks were greater than those in the 2% KA + 0.1% SDM group and an adenoma was observed in a rat at the end of the recovery period, no development of carcinomas was evident at either time point. No thyroid proliferative lesions were induced in the group given 2% KA for the initial 8 weeks only. The results of the present studies indicate that KA has neither in vivo genotoxic potential nor tumor initiation activity in the thyroid, and strongly suggest that the earlier observed thyroid tumorigenic activity of KA is attributable to a non-genotoxic mechanism. 相似文献
537.
Absence of liver tumor-initiating activity of kojic acid in mice 总被引:2,自引:0,他引:2
In order to evaluate the tumor-initiating activity of kojic acid (KA) in mouse liver, an in vivo initiation assay in liver was performed using partially hepatectomized mice. Male ICR mice were fed on a basal diet (BD) containing 0 or 3% KA for 4 weeks, followed by distilled water (DW) containing 0 or 500 ppm phenobarbital (PB) for 13 weeks. Two weeks after the treatment with PB, two-thirds partial hepatectomy was preformed in all mice in order to enhance the regeneration and proliferating activities of the hepatocytes. In microscopic examinations, no proliferative lesion was observed in any of the groups. There were no differences in the number of γ-glutamyltransferase-positive cells, an expected marker for preneoplastic hepatocytes in mice, between the KA + DW and the KA + PB groups. In the immunohistochemical analyses of the proliferating activity of hepatocytes, significant increases in the labeling index of proliferating cell nuclear antigen (PCNA) were observed in the BD + PB and KA + PB groups as compared to the BD + DW group; however, no significant difference in the positivity of PCNA was observed between the BD + PB and the KA + PB groups. These results of the present study suggest the possibility that KA has no tumor-initiating activity in the liver of mice. 相似文献
538.
Antimony is classified as "possibly carcinogenic to humans" and there is also sufficient evidence for antimony carcinogenicity in experimental animals. Stibine is a volatile inorganic antimony compound to which humans can be exposed in occupational settings (e.g., lead-acid battery charging). Because it is highly toxic, stibine is considered a significant health risk; however, its genotoxicity has received little attention. For the work reported here, stibine was generated by sodium borohydride reduction of potassium antimony tartrate. Trimethylstibine is a volatile organometallic antimony compound found commonly in landfill and sewage fermentation gases at concentrations ranging between 0.1 and 100 microg/m3. Trimethylstibine is generally considered to pose little environmental or health risk. In the work reported here, trimethylstibine was generated by reduction of trimethylantimony dichloride using either sodium borohydride or the thiol compounds, dithioerythritol (DTE), L-cysteine, and glutathione. Here we report the evaluation of the in vitro genotoxicities of five antimony compounds-potassium antimony tartrate, stibine, potassium hexahydroxyantimonate, trimethylantimony dichloride, and trimethylstibine-using a plasmid DNA-nicking assay. Of these five antimony compounds, only stibine and trimethylstibine were genotoxic (significant nicking to pBR 322 plasmid DNA). We found stibine and trimethylstibine to be about equipotent with trimethylarsine using this plasmid DNA-nicking assay. Reaction of trimethylantimony dichloride with either glutathione or L-cysteine to produce DNA-damaging trimethylstibine was observed with a trimethylantimony dichloride concentration as low as 50 microM and L-cysteine or glutathione concentrations as low as 500 and 200 microM, respectively, for a 24 h incubation. 相似文献
539.
Lopes LF Piccoli Fde S Paixão VA Latorre Mdo R Camargo Bd Simpson AJ Caballero OL 《Leukemia research》2004,28(12):1281-1286
Cancer patients receiving chemotherapy are exposed to high doses of cytotoxic and genotoxic drugs which, in some cases, can lead to treatment related leukemia. Since this only occurs in a minority of patients, however, it is possible some individuals are predisposed due to genetic polymorphisms in genes for enzymes that mediate drug metabolism. To address this possibility we measured the genotoxicity of chemotherapeutic agents in patients receiving treatment for ALL by the frequency of the Vγ/Jβ trans-rearrangement in their peripheral blood leukocytes and compared this with CYP3A4 genotype. CYP3A4 is the most abundant of the cytochrome P450 (CYP) enzyme in the liver and intestine which contains a common −392A>G substitution in the promoter region (CYP3A4*1B allele). We found a significant increase in the frequency of rearrangements during chemotherapy only in patients homozygous for the wild type CYP3A4*1A allele. This provides a direct link between CYP3A4 genotype and susceptibility to drug genotoxicity thus strengthening the possibility that predisposition to treatment related leukemia may be measurable by simple genetic testing. 相似文献
540.
Hideki Mori Shigeyuki Sugie Naoki Yoshime Hitoshi Iwata Akiyoshi Nishikawa Kogen Matsukubo Hidesuke Shimizu Iwao Hirono 《Cancer science》1988,79(2):204-211
The genotoxicity of a variety of hydrazine derivatives was examined in the DNA-repair test on rat or mouse hepatocytes. Out of 32 hydrazine derivatives, 6 chemicals, i.e., N -acetyl-4-(hydroxymethyl)phenylhydrazine, 1,2-dimethylhydrazine - 2HCl, 1-hydrazinophthalazine - HCl, methylhydrazine-sulfate, p, p '-oxybisbenzene disulfonylhydrazide and phenylhydrazine-HCl, elicited positive DNA repair responses in the test on rat hepatocytes. In the test on mouse hepatocytes, 4 more hydrazine derivatives, i.e., 1,1-dimethylhydrazine, hydrazine hydrate, hydrazine sulfate and 2-methyl-4-chlorophenoxyacetic acid hydrazide-HCl also generated positive responses, in addition to the 6 positive compounds in the rat assay. These results suggest that mouse hepatocytes are more susceptible to the genotoxicity of hydrazine derivatives, and that the species differences in genotoxicity appear to he in agreement with the in vivo carcinogenicity of these agents. 相似文献