全文获取类型
收费全文 | 79642篇 |
免费 | 6832篇 |
国内免费 | 3107篇 |
专业分类
耳鼻咽喉 | 547篇 |
儿科学 | 1203篇 |
妇产科学 | 2138篇 |
基础医学 | 17710篇 |
口腔科学 | 2195篇 |
临床医学 | 5946篇 |
内科学 | 10231篇 |
皮肤病学 | 1773篇 |
神经病学 | 3904篇 |
特种医学 | 2409篇 |
外国民族医学 | 23篇 |
外科学 | 4683篇 |
综合类 | 10964篇 |
现状与发展 | 17篇 |
一般理论 | 12篇 |
预防医学 | 6148篇 |
眼科学 | 1180篇 |
药学 | 8511篇 |
21篇 | |
中国医学 | 1881篇 |
肿瘤学 | 8085篇 |
出版年
2024年 | 68篇 |
2023年 | 907篇 |
2022年 | 1230篇 |
2021年 | 2574篇 |
2020年 | 2227篇 |
2019年 | 2225篇 |
2018年 | 2128篇 |
2017年 | 2395篇 |
2016年 | 2609篇 |
2015年 | 2872篇 |
2014年 | 4189篇 |
2013年 | 5675篇 |
2012年 | 4016篇 |
2011年 | 4614篇 |
2010年 | 3882篇 |
2009年 | 3806篇 |
2008年 | 3745篇 |
2007年 | 3896篇 |
2006年 | 3741篇 |
2005年 | 3450篇 |
2004年 | 3178篇 |
2003年 | 2839篇 |
2002年 | 2445篇 |
2001年 | 2227篇 |
2000年 | 1896篇 |
1999年 | 1631篇 |
1998年 | 1587篇 |
1997年 | 1460篇 |
1996年 | 1370篇 |
1995年 | 1300篇 |
1994年 | 1232篇 |
1993年 | 1006篇 |
1992年 | 962篇 |
1991年 | 798篇 |
1990年 | 669篇 |
1989年 | 607篇 |
1988年 | 543篇 |
1987年 | 383篇 |
1986年 | 369篇 |
1985年 | 565篇 |
1984年 | 475篇 |
1983年 | 281篇 |
1982年 | 335篇 |
1981年 | 287篇 |
1980年 | 239篇 |
1979年 | 165篇 |
1978年 | 154篇 |
1977年 | 96篇 |
1976年 | 95篇 |
1975年 | 42篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
101.
Mitsumasa Iwata Shunji Izuta Motoshi Suzuki Kiyohide Kojima Yoshihito Furuhashi Yutaka Tomoda Shonen Yoshida 《Cancer science》1991,82(4):433-439
We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (-)-( R )-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis- diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP. 相似文献
102.
本实验用~3H-TdR掺入,液体闪烁测量法测定细胞DNA期外合成的方法,测定了小鼠和大鼠的肠淋巴结细胞、人和大鼠外周血淋巴细胞、S-180V肿瘤细胞等经紫外线照射后的UDS,观察到UDS掺入量随辐照度增加而增加。在同一辐照剂量下,以小鼠肠淋巴结细胞的UDS值最高,其次是人外周血淋巴细胞和S-180V肿瘤细胞,而大鼠外周血淋巴细胞和肠淋巴结细胞最低。 相似文献
103.
104.
二乙酰二脱水卫矛醇对小鼠白血病L1210细胞增殖的影响 总被引:5,自引:0,他引:5
目的 研究二乙酰二脱水卫矛醇 (1 ,2 :5 ,6 dianhydro 3 ,4 diacetylgalactitol,DADAG)的抗脑白血病作用及机制。方法 用小鼠脑内移植瘤模型、MTT法、DNA掺入法、流式细胞仪和Westernblot法 ,观察DADAG对小鼠脑内移植瘤和体外白血病L1 2 1 0 细胞的作用 ,并探讨作用机制。结果 DADAG对DBA/ 2小鼠脑内移植白血病L1 2 1 0 有明显的抑制作用 ;对体外白血病L1 2 1 0 细胞同样有很强的抗增殖作用 ,其IC50 值为 2 4 6mg·L- 1 。DADAG不可逆地抑制L1 2 1 0 细胞内DNA的生物合成。DADAG 2 4mg·L- 1 处理L1 2 1 0 细胞 6h后 ,细胞发生G2 /M周期阻滞 ,2 4h后达最高峰。细胞周期素B1 蛋白水平在DADAG处理 2 4h后开始下降 ,而磷酸化的细胞周期依赖性激酶CDK1在DADAG处理 6h后开始上调 ,并呈时间依赖性。结论 DADAG的抗脑白血病作用与其抑制白血病细胞的增殖密切相关 相似文献
105.
目的 克隆人胃癌细胞端粒酶RNA组分(hTR)基因片段并构建其正义和反义真核表达载体,研究反义端粒酶RNA对人胃癌细胞株MKN-45端粒酶活性的影响。方法 采用RT-PCH方法从人胃癌细胞株MKN-45中扩增出人hTR部分cDNA序列,将该片段分别正向和反向插入PEF6/V5-His-TOPO载体后构建人端粒酶RNA组分(hTR)基因正、反义真核表达载体,随后采用脂质体转染法将该正、反义载体转染入人胃癌细胞株MKN-45,用TRAP法观察后者端粒酶活性的改变。结果 所克隆的基因片段其碱基序列与文献报导完全一致,且插入载体的方向完全正确。与正常对照、转染正义载体、空载体者比较,转染反义载体者端粒酶活性显著下降。结论 本实验已成功克隆了人端粒酶RNA组分(hTR)基因的部分序列并成功构建hTR正反义真核表达载体,而且反义端粒酶RNA能有效降低人胃癌细胞株MKN-45端粒酶活性。 相似文献
106.
W. A. A. Tjalma M. Arbyn† J. Paavonen‡ T. R. Van Waes & J. J. Bogers§ 《International journal of gynecological cancer》2004,14(5):751-761
Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines. 相似文献
107.
Pilar Nicolás 《Hereditary cancer in clinical practice》2007,5(3):144-152
The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing. 相似文献
108.
L.J. Mackintosh† M.N.C. de Koning‡ W.G.V. Quint‡ J. ter Schegget‡ I.M. Morgan R.M. Herd† M.S. Campo 《The British journal of dermatology》2009,161(1):56-62
Background Nonmelanoma skin cancer (NMSC) has been linked to cutaneous human papillomaviruses of the genus beta (betaPV).
Objectives We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients.
Methods One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction–reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes.
Results In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples ( P = 0·046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2–8). Tumours from IS patients were from a younger age group (mean age 57·4 years) than IC patients (mean age 73·8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) ( P < 0·001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin.
Conclusions A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis. 相似文献
Objectives We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients.
Methods One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction–reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes.
Results In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples ( P = 0·046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2–8). Tumours from IS patients were from a younger age group (mean age 57·4 years) than IC patients (mean age 73·8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) ( P < 0·001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin.
Conclusions A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis. 相似文献
109.
110.
Occhiuto F Palumbo DR Samperi S Zangla G Pino A De Pasquale R Circosta C 《Phytotherapy research : PTR》2009,23(2):192-196
Oxidative stress-induced neuronal cell death has been implicated in different neurological disorders and neurodegenerative diseases such as Alzheimer's disease and Parkinson's. Using the Alzheimer's disease-associated hydrogen peroxide (H(2)O(2)), we investigated the neuroprotective efficacy of a natural mixture of phytoestrogenic isoflavones (genistein, daidzein, biochanin A and formononetin) from Trifolium pratense L. (Red clover) against oxidative stress-induced cell death in human cortical cell line HCN 1-A maintained in culture. Neuronal viability was determined by MTT or trypan blue test and neuronal integrity by morphological analysis.The results obtained indicate that exposure of HCN 1-A cell cultures to hydrogen peroxide resulted in a concentration-dependent decrease in neuron viability. Concentration of H(2)O(2) ranging from 50 to 200 microg/ml were toxic to these cultures. A 24-hour pretreatment with 0.5, 1 and 2 microg/ml isoflavones extract significantly increased cell survival as evidenced by MTT or trypan blue test and significantly prevented the morphological disruption caused by H(2)O(2) as shown by microscopical inspection, indicating that neurons treated with isoflavones were protected from the cell death induced by H(2)O(2) exposure. These findings imply that the neuroprotective effect of isoflavones extract is partly associated with its antioxidant activity. Further, results of these investigations indicate that although isoflavones extract exert a neuroprotective effect, it do not promoted cortical neuron process outgrowth. 相似文献