全文获取类型
收费全文 | 41996篇 |
免费 | 2536篇 |
国内免费 | 1326篇 |
专业分类
耳鼻咽喉 | 209篇 |
儿科学 | 733篇 |
妇产科学 | 502篇 |
基础医学 | 5767篇 |
口腔科学 | 705篇 |
临床医学 | 2404篇 |
内科学 | 6354篇 |
皮肤病学 | 651篇 |
神经病学 | 3772篇 |
特种医学 | 817篇 |
外国民族医学 | 4篇 |
外科学 | 2713篇 |
综合类 | 5601篇 |
预防医学 | 1806篇 |
眼科学 | 402篇 |
药学 | 7174篇 |
3篇 | |
中国医学 | 4056篇 |
肿瘤学 | 2185篇 |
出版年
2023年 | 357篇 |
2022年 | 771篇 |
2021年 | 885篇 |
2020年 | 821篇 |
2019年 | 1622篇 |
2018年 | 1487篇 |
2017年 | 1182篇 |
2016年 | 919篇 |
2015年 | 1001篇 |
2014年 | 1717篇 |
2013年 | 2191篇 |
2012年 | 1937篇 |
2011年 | 2223篇 |
2010年 | 1944篇 |
2009年 | 1900篇 |
2008年 | 1968篇 |
2007年 | 1959篇 |
2006年 | 1750篇 |
2005年 | 1396篇 |
2004年 | 1414篇 |
2003年 | 1397篇 |
2002年 | 1144篇 |
2001年 | 1158篇 |
2000年 | 902篇 |
1999年 | 859篇 |
1998年 | 684篇 |
1997年 | 613篇 |
1996年 | 487篇 |
1995年 | 402篇 |
1994年 | 360篇 |
1993年 | 306篇 |
1992年 | 236篇 |
1991年 | 239篇 |
1990年 | 195篇 |
1989年 | 205篇 |
1988年 | 149篇 |
1987年 | 149篇 |
1985年 | 711篇 |
1984年 | 992篇 |
1983年 | 741篇 |
1982年 | 717篇 |
1981年 | 673篇 |
1980年 | 542篇 |
1979年 | 524篇 |
1978年 | 383篇 |
1977年 | 266篇 |
1976年 | 354篇 |
1975年 | 316篇 |
1974年 | 239篇 |
1973年 | 221篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
151.
背景与目的:探讨莱菔硫烷对人膀胱癌细胞(T24)细胞周期的影响及作用机制。材料与方法:采用噻唑蓝(MTT)法研究不同浓度的莱菔硫烷对T24细胞生长的抑制作用并测定其半数抑制浓度(IC50);采用流式细胞仪检测莱菔硫烷对T24细胞周期的影响;采用westernblot研究莱菔硫烷对T24细胞中细胞周期蛋白依赖激酶抑制剂P16和P27的表达情况。结果:在较低剂量范围内(≤40μmol/L),随着作用剂量的增加,莱菔硫烷对T24细胞的生长的抑制作用也明显增强。10、20、40μmol/L莱菔硫烷的抑制率分别为(12.5±3.95)%,(25.0±2.50)%、(50.0±5.33)%;在较高剂量(60μmol/L~160μmol/L)时,这种抑制作用不再呈剂量依赖性;莱菔硫烷作用72h后的IC50值为(51.12±7.10)μmol/L;莱菔硫烷能使T24细胞周期阻滞于G0/G1期,20μmol/L莱菔硫烷作用48h后,在G0/G1峰之前出现凋亡峰;20μmol/L莱菔硫烷作用于T24细胞8、12、24h后能明显诱导P27蛋白的表达,作用早期(8h)时能诱导P16蛋白的表达。结论:莱菔硫烷能抑制T24细胞生长并使该细胞周期阻断在G0/G1期,其作用机制主要是通过诱导P27蛋白及早期诱导P16蛋白来实现的。 相似文献
152.
对生长在合作地区的955名藏、汉族学生进行了个性特征及其影响因素的调查探讨。结果表明:本民族间男、女生E分比较,男生低于女生,显示女生性格较男生性格外向倾向性大。稳定性方面女生N分高于男生,即女生情绪一般不及男生稳定。此外与该地区藏汉族学生个性特征关系较为密切的因素是:兄弟姐妹数、父母亲文化程度、职业以及学前教育和智商。 相似文献
153.
Dagmar Busse Jose Cosme Philippe Beaune Heyo K. Kroemer Michel Eichelbaum D. Busse H. K. Kroemer M. Eichelbaum 《Naunyn-Schmiedeberg's archives of pharmacology》1995,353(1):116-121
The calcium channel blocker verapamil [2,8-bis-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] undergoes extensive biotransformation in man. We have previously demonstrated cytochrome P450 (CYP) 3A4 and 1A2 to be the enzymes responsible for verapamil N-dealkylation (formation of D-617 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile]), and verapamil N-demethylation (formation of norverapamil [2,8-bis(3,4-dimethoxyphenyl)-2-isopropyl-6-azaoctanitrile]), while there was no involvement of CYP3A4 and CYP1A2 in the third initial metabolic step of verapamil, which is verapamil O-demethylation. This pathway yields formation of D-703 [2-(4-hydroxy-3-methoxyphenyl)-8-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] and D-702 [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)6-methyl-2-isopropyl-6-azaoctanitrile]. The enzymes catalyzing verapamil O-demethylation have not been characterized so far. We have therefore identified and characterized the enzymes involved in verapamil O-demethylation in humans by using the following in vitro approaches: (I) characterization of O-demethylation kinetics in the presence of the microsomal fraction of human liver, (II) inhibition of verapamil O-demethylation by specific antibodies and selective inhibitors and (111) investigation of metabolite formation in microsomes obtained from yeast strain Saccharomyces cerevisiae W(R), that was genetically engineered for stable expression of human CYP2C8, 2C9 and 2C18.In human liver microsomes (n=4), the intrinsic clearance (CLint), as derived from the ratio of V
max/Km, was significantly higher for O-demethylation to D-703 compared to formation of D-702 following incubation with racemic verapamil (13.9±1.0 vs 2.4±0.6 ml*min-1
*g-1 mean±SD; p<0.05), S-Verapamil (16.8±3.3 vs 2.2±1.2 ml* mini*g-1, p<0.05) and R-verapamil (12.1±2.9 vs 3.6 ±1.3 ml*min-1
* g-1; p<0.05), thus indicating regioselectivity of verapamil O-demethylation process. The CLint of D-703 formation in human liver microsomes showed a modest but significant degree of stereo selectivity (p<0.05) with a S/R-ratio of 1.41±0.17. Anti-LKM2 (anti-liver/kidney microsome) autoantibodies (which inhibit CYP2C9 and 2C19) and sulfaphenazole (a specific CYP2C9 inhibitor) reduced the maximum rate of formation of D-703 by 81.5±4.5% and 45%, that of D-702 by 52.7±7.5% and 72.5%, respectively. Both D-703 and D-702 were formed by stably expressed CYP2C9 and CYP2C18, whereas incubation with CYP2C8 selectively yielded D-703.In conclusion, our results show that enzymes of the CYP2C subfamily are mainly involved in verapamil O-demethylation. Verapamil therefore has the potential to interact with other drugs which inhibit or induce these enzymes. 相似文献
154.
Purpose. The inhibitory effects of omeprazole on diazepam metabolism in vitro and in vivo are compared in the rat.
Methods. 3-hydroxylation and N-demethylation of diazepam was investigated in the presence of a range of omeprazole concentrations (2-500µM) in hepatic microsomes and hepatocytes. Zero order infusions together with matched bolus doses of omeprazole were used to achieve a range of steady state plasma concentrations (10-50mg/ L) and to study the diazepam-omeprazole interaction in vivo.
Results. The 3-hydroxlation pathway was more prone to inhibition (KIs 108 ± 30 and 28 ± 11 µM in microsomes and hepatocytes, respectively) than the demethylation pathway (KIs of 226 ± 76 and 59 ± 27 µM in microsomes and hepatocytes, respectively). In both in vitro systems, the mechanism of inhibition was competitive with Km/KI ratios larger than 1 for the 3HDZ pathway and smaller than 1 for the NDZ pathway. There was an omeprazole concentration dependent decrease in diazepam clearance in vivo which could be modelled using a simple inhibition equation with a KI of 57µM (19.8mg/L). In contrast there was no statistically significant change in the steady state volume of distribution for diazepam in the presence of omeprazole.
Conclusions. The in vivo KI for the omeprazole: diazepam inhibition interaction shows closer agreement with the KI values obtained in hepatocytes than with those observed in microsomes. 相似文献
155.
156.
N. I. Triantafyllou K. Voumvourakis I. Zalonis K. Sfagos V. Mantouvalos S. Malliara C. Papageorgiou 《Acta neurologica Scandinavica》1992,85(1):10-13
Auditory event-related potentials (AERP) were elicited in 47 patients with relapsing-remitting (RR) multiple sclerosis (MS) and 24 age-matched controls. MS patients had significantly prolonged N2 and P3 latencies as well as low P3 amplitude compared with controls. Seven of them exceeded 3 standard deviations from the control mean values. The observed N2 and P3 alterations are associated with the patients' disability status as it is defined by the Kurtzke expanded disability status scale (EDSS), but are not related to the duration of the disease. A possible cognitive decline as reflected in the observed AERP components alterations in MS patients is subsequently discussed. 相似文献
157.
胃癌组织中KAI1、nm23及P53的表达及其临床意义 总被引:5,自引:4,他引:1
目的:探讨正常胃黏膜、不典型增生胃黏膜及癌组织中KAI1、nm23及P53蛋白的表达.方法:应用SP法免疫组化检测22例正常胃黏膜,65例不典型增生胃黏膜及74N胃癌组织中的KAI1、nm23及P53蛋白的表达.结果:正常胃黏膜、不典型增生胃黏膜及胃癌组织中,KAI1和nm23阳性率呈降低趋势,组间差异性有统计学意义(x2=20.885, P<0.001;x2=29.133,P<0.05):P53蛋白阳性表达率呈增加趋势,组间差异性有统计学意义(x2=21.954,P<0.001).Fisher精确概率检验显示:在胃癌组中不同的浸润深度、有无淋巴结转移和脉管侵犯组内KAI1、nm23及 P53组阳性表达率的差异性有统计学意义(x2 =20.885,P<0.001;x2=29.133,P<0.05;x2= 21.954,P<0.001);而在年龄、性别组间的差异性无统计学意义.Spearman等级相关分析显示 KAI1与nm23表达呈正相关(r=0.859,P<0.05); KAI1与P53表达呈负相关(r=-0.859,P<0.05), nm23与P53表达呈负相关(r=-0.874,P<0.05) 结论:抑癌基因KAI1与nm23的缺失以及P53 蛋白的过表达可能是胃癌发生、发展及浸润和转移的重要原因之一. 相似文献
158.
(1)目的 研究5型腺病毒载体(Ad5)携带P16基因对恶性脑胶质瘤细胞系TJ899生长状态的影响。(2)方法 免疫组化(SP法)测定P16蛋白表达,MTT(methly thiazolyl tetrazolium,MTT)法测定恶性脑胶质瘤细胞系生长状态,克隆形成实验。(3)结果 重组体腺病毒能介导P16外源基因在恶性脑胶质瘤细胞系TJ899细胞中阳性表达,6d时肿瘤细胞生长抑制率为93%,并且能显地抑制肿瘤细胞的克隆形成能力。(4)结论 腺病毒介导P16基因能在肿瘤细胞中表达。并能明显抑制肿瘤细胞生长的状态。 相似文献
159.
Heukrodt Carol; Powazek Morris; Brown Warren S.; Kennelly Denise; Imbus Charles; Robinson Herb; Schantz Stacy 《Journal of pediatric psychology》1988,13(2):223-236
The long-term effects of disease and treatment on electrophysiologicalmeasures of neurocognitive function were studied in childrenwho had survived acute lymphoblastic leukemia (ALL) for at least4 years and were currently in remission. We report here changesin cognitive processing time as shown by the latency of theP3 wave of the auditory event-related EEG potential (ERP). P3latency was significantly prolonged in long-term ALL surivors,as well as in patients successfully trreated for solid tumors(ST)outside the CNS who received similar chemotherapy but did notreceive prophylactic treatment to the CNS. P3 latencies werestrongly correlated with measures of school performance andIQ in these individuals. The similarity in P3 latency betweenthe ALL and ST groups suggests that the treatments used on thesepateints produce changes in electrophysiological responses thatare associated with mild, but significant, cognitive deficits. 相似文献
160.
更年期妇女生理心理健康状况探讨 总被引:26,自引:2,他引:24
目的探讨更年期妇女生理、心理健康状况及相互关系 ,为进一步缓解更年期妇女的症状提供医疗和护理上的依据。方法对北京大学第一临床医院更年期门诊病人进行问卷调查 ,数据结果应用SPSS 8 0数据分析软件包进行处理。结果更年期妇女Kupperman总体平均分为 2 0 12± 9 97分 ,SCL 90评分量表总体平均分为 4 6 6 2±36 2 8分 ,并且以潮热出汗、失眠等躯体症状 ,以及强迫症状、人际关系敏感、抑郁、焦虑等心理症状表现突出。应用激素替代疗法后 ,能有效缓解更年期妇女潮热出汗、抑郁心烦、疲乏、骨关节痛、敌对的症状 ,与未用激素替代疗法者有显著差异。对更年期妇女的生理、心理进行分析显示 ,更年期妇女生理心理症状呈中等程度相关性 (r=0 6 17,P <0 0 0 1)。结论医护人员应加强对更年期妇女生理心理双方面的关注。 相似文献