全文获取类型
收费全文 | 23817篇 |
免费 | 2113篇 |
国内免费 | 847篇 |
专业分类
耳鼻咽喉 | 98篇 |
儿科学 | 515篇 |
妇产科学 | 280篇 |
基础医学 | 4264篇 |
口腔科学 | 362篇 |
临床医学 | 1334篇 |
内科学 | 3820篇 |
皮肤病学 | 476篇 |
神经病学 | 1392篇 |
特种医学 | 582篇 |
外国民族医学 | 2篇 |
外科学 | 2475篇 |
综合类 | 2722篇 |
现状与发展 | 1篇 |
预防医学 | 1333篇 |
眼科学 | 221篇 |
药学 | 3780篇 |
2篇 | |
中国医学 | 924篇 |
肿瘤学 | 2194篇 |
出版年
2024年 | 51篇 |
2023年 | 632篇 |
2022年 | 1484篇 |
2021年 | 1239篇 |
2020年 | 1058篇 |
2019年 | 1240篇 |
2018年 | 1138篇 |
2017年 | 970篇 |
2016年 | 833篇 |
2015年 | 997篇 |
2014年 | 1409篇 |
2013年 | 1457篇 |
2012年 | 1311篇 |
2011年 | 1420篇 |
2010年 | 1100篇 |
2009年 | 1010篇 |
2008年 | 944篇 |
2007年 | 871篇 |
2006年 | 769篇 |
2005年 | 821篇 |
2004年 | 733篇 |
2003年 | 601篇 |
2002年 | 387篇 |
2001年 | 353篇 |
2000年 | 298篇 |
1999年 | 271篇 |
1998年 | 240篇 |
1997年 | 235篇 |
1996年 | 198篇 |
1995年 | 211篇 |
1994年 | 154篇 |
1993年 | 133篇 |
1992年 | 88篇 |
1991年 | 93篇 |
1990年 | 72篇 |
1989年 | 73篇 |
1988年 | 62篇 |
1987年 | 60篇 |
1986年 | 65篇 |
1985年 | 195篇 |
1984年 | 286篇 |
1983年 | 181篇 |
1982年 | 195篇 |
1981年 | 184篇 |
1980年 | 134篇 |
1979年 | 130篇 |
1978年 | 103篇 |
1977年 | 75篇 |
1976年 | 65篇 |
1975年 | 49篇 |
排序方式: 共有10000条查询结果,搜索用时 2 毫秒
51.
52.
Otagiri Masaki Yamamichi Ryuji Marayama Toru Imai Teruko Suenaga Ayaka Imamura Yorishige Kimachi Kazuhiko 《Pharmaceutical research》1989,6(2):156-159
The interactions of acidic and basic drugs with 1-acid glycoprotein (1-AGP) were investigated using circular dichroism (CD) measurements. Extrinsic Cotton effects were generated by the binding of drugs to 1-AGP. The CD data suggested the presence of a single binding site on the 1-AGP molecule. The induced ellipticities of the acidic drug–1-AGP system decreased with increasing pH, while the ellipticities for the basic drugs increased with pH. The ellipticities for all drugs were reduced by the addition of fatty acids. Furthermore, the induced ellipticities decreased in the presence of cesium chloride for basic drugs bound to 1-AGP. The extrinsic Cotton effects therefore appear to result from hydrophobic interaction with 1-AGP for the acidic drugs and from hydrophobic and electrostatic interactions for the basic drugs. 相似文献
53.
54.
Smad7过度表达抑制3T3细胞增殖和TGF-β1基因表达 总被引:3,自引:1,他引:3
研究Smad7过度表达对TGF β1基因表达的调控和对 3T3细胞增殖的影响。实验将Smad7质粒 ,通过脂质体介导转染NIH3T3细胞 ,应用RT PCR方法鉴定转染结果和检测TGF β1mRNA的表达 ,以及用免疫细胞化学检测TGF β1蛋白的表达情况 ,并观察基因转染对细胞增殖的影响。结果显示转染Smad7后 ,NIH3T3细胞中TGF β1mRNA的表达显著减少 (P <0 0 5 ) ,TGF β1蛋白的表达下降 ,细胞增殖明显减缓 (P <0 0 5 )。提示Smad7过度表达能够抑制 3T3细胞的增殖和TGF β1基因的表达 ,可以通过阻断TGF β细胞内信号传导来调控TGF β1的生物学行为。 相似文献
55.
目的探讨细胞毒性T淋巴细胞相关抗原4融合蛋白(CTLA-4Ig)对活动期狼疮肾炎(LN)患者外周血单个核细胞(PBMC)细胞表面B7-1(CD80)和B7-2(CD86)表达的影响及其对抗双链DNA(dsDNA)抗体和免疫球蛋白产生的影响。方法将18例活动期LN患者的抗凝血标本随机分为LN的CTLA-4Ig处理组(LN-T组9例)和普通培养组(LN-NC组9例)。另以14例正常人的抗凝血标本为对照,随机分为正常人的CTLA-4Ig处理组(NC-T组7例)和普通培养组(NC-NC组7例)。用密度梯度离心法分离PBMC。处理组加入CTLA-4Ig(10ng/L)、普通培养组加入等量普通培养基37℃孵育72h后,采用流式细胞仪技术检测PBMC细胞表面B7-1和B7-2分子的表达;ELISA法检测孵育液中抗dsDNA抗体、IgG及IgM水平。结果活动期LN患者CTLA-4Ig处理组与普通培养组比较,PB-MC表面B7-2分子表达明显下降(P<0.01);B7-1分子表达无显著变化(P>0.05);孵育液中抗dsD-NA抗体、IgG及IgM的生成均明显减少(P<0.01)。而正常人的两组间各指标差异均无统计学意义(P>0.05)。结论CTLA-4Ig可抑制活动期LN患者的PBMC表面B7-2分子的表达,并可减少其抗dsDNA抗体、IgG及IgM的分泌。 相似文献
56.
Yamamoto R Isobe T Eguchi T Tang WR Kiyokawa N Amemiya H Fujimoto J Sato E Takagaki Y Yasue H 《Molecular immunology》2005,42(12):1485-1493
Complete porcine CD3ζ-chain cDNA sequence was obtained for the first time, and its genomic nucleotide sequence was investigated from exon 2 down to CD3η-chain exon 8. The sequence of porcine CD3ζ-chain showed homologous amino acid sequence with human and murine counterparts, in contrast to CD3η-chain exon 8 with diversity among animals previously investigated. CD3η-chain peptide is an alternative splice form of CD3ζ-chain exon 7 splicing to CD3η-chain exon 8 instead of CD3ζ-chain exon 8. The genomic sequences revealed that the splice acceptor sequences of CD3η-chain exon 8 of all animals investigated to be completely uniform. Further, CD3η-chain exon 8 amino acid sequences retained the unique characters of having high proline (Pro) and positively charged amino acid content except for rats and mice. Although the biological role of CD3η-chain remains to be enigmatic, these evidences suggests the evolutional pressure to maintain its sequence. 相似文献
57.
Pelosi G Scarpa A Veronesi G Spaggiari L Del Curto B Moore PS Maisonneuve P Sonzogni A Masullo M Viale G 《Virchows Archiv : an international journal of pathology》2005,447(6):969-977
Nuclear translocation of β-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation
in nonsmall cell lung cancer. Less is known on β-catenin transactivation in high-grade pulmonary neuroendocrine tumors and
on the status of β-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or β-catenin target genes
cyclin D1 and matrix metalloproteinase-7 (MMP-7). β-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine
carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for β-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. β-catenin was
expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed
immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining
along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated
with EGFR and HER-2 protein expression. β-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and
two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These
cases, however, did not show β-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear β-catenin and
any clinicopathological variable including patients' survival. The subcellular compartmentalization of β-catenin is profoundly
altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows β-catenin nuclear accumulation
in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification
or expression.
The authors have no significant financial or other relationship with the manufacturers of any commercial products or commercial
services presented in this paper 相似文献
58.
目的 研究鼠巨细胞病毒(MCMV)感染对体外培养神经干细胞(NSCs)分化及分化基因表达的影响,探讨CMV先天感染致神经损伤的机制.方法 体外分离培养和鉴定BALB/c胎鼠NSCs并检测其分化潜能,用感染复数(MOI)为5、1和0.1的MCMV Smith毒株感染NSCs并进行分化培养,倒置显微镜下观察细胞形态学改变,流式细胞术检测分化细胞比率,免疫荧光法观察NSCs及其分化细胞标记物Nestin、胶质纤维酸性蛋白(GFAP)和神经元特异性烯醇化酶(NSE)表达的变化,采用MCMV早期抗原(EA)示踪感染过程(MOI=1),real-time RT-PCR检测分化早期NSCs Wnt信号途径关键分化基因Wnt-3和Wnt-Ta mRNA水平的动态变化.结果 体外培养的NSCs呈球样生长,神经干细胞特异性标记Nestin表达阳性,并可进一步诱导分化为NF-200阳性的神经元和GFAP阳性的星形胶质细胞;分化培养后,感染组NSCs不能贴壁分化生长并逐渐出现肿胀,细胞Nestin表达下调缓慢并显著高于正常对照组,而GFAP和NSE表达显著低于正常对照组(P<0.05),可检测到MCMV EA的阳性表达;分化培养3-9 d,感染组Nestin阳性细胞比率显著高于正常对照组,GFAP和NSE阳性细胞比率显著低于正常对照组(P<0.05);感染组Wnt-3 mRNA水平在分化培养后第1~2天显著低于正常对照组(P<0.05),感染组Wnto-7a mRNA水平在第0.5~2天明显低于正常对照组(P<0.05);感染组和正常对照组的差异随病毒MOI的增加而更加明显.结论 MCMV感染可明显抑制NSCs向神经元和星形胶质细胞方向分化,导致分化细胞比率减少;下调或干扰NSCs wnt信号途径分化基因wnt-3和Wnt-7a的表达;抑制NSCs分化及其分化基因表达的效应与MOI大小存在一定量效依赖关系;MCMV可能通过抑制NSCs分化基因的表达来抑制其分化,这可能是CMV先天感染致脑发育异常的重要机制之一. 相似文献
59.
Luigi Marazzini Andrea Pelucchi Marina Bozzoni Berardino Mastropasqua Erminio Longhini 《Journal of clinical immunology》1985,5(3):195-203
The role of adrenergic mechanism in the pathogenesis of allergic disease is controversial. Recent experimental and clinical reports have suggested that -adrenergic blockade impairs and stimulation enhances extrarenal potassium uptake in humans. This led us to study the effect of the intravenous administration of salbutamol, a specific -2-adrenergic agonist, on serum potassium in 9 healthy subjects and in 23 patients with allergic asthma and/or rhinitis. Serum potassium fell significantly and reached a peak decline at the end of venous infusion in all the normal subjects. Seventeen atopic subjects showed a lower or absent serum K+ decrement: there was no difference between asthmatic and rhinitic patients. There was no relation among the salbutamol-induced serum potassium decrement, serum glucose increment, blood pressure and heart-rate changes, and nonspecific bronchial reactivity. These findings suggest that -2-adrenergic hyporesponsiveness is present only in some allergic patients. 相似文献
60.
Angiotensin-(1–7) stimulates water transport in rat inner medullary collecting duct: evidence for involvement of vasopressin V2 receptors 总被引:1,自引:0,他引:1
Magaldi AJ Cesar KR de Araújo M Simões e Silva AC Santos RA 《Pflügers Archiv : European journal of physiology》2003,447(2):223-230
The peptide angiotensin-(1–7) [Ang-(1–7)] is known to enhance water transport in rat inner medullary collecting duct (IMCD). The aim of this study was to determine the mechanism of the Ang-(1–7) effect on osmotic water permeability (P
f). P
f was measured in the normal rat IMCD perfused in vitro in presence of agonists [Ang-(1–7), arginine vasopressin (AVP) and Ang-(3–8)], and antagonists of the angiotensin and the vasopressin cascade. Ang-(1–7), but not Ang-(3–8), increased P
f significantly. The effect of Ang-(1–7) on P
f was abolished by its selective antagonist, A-779, added before or after Ang-(1–7). Prostaglandin E2 and the protein kinase A inhibitor H8 also blocked the Ang-(1–7) effect. Blockade of vasopressin V1 receptors by antagonists did not change the Ang-(1–7) effect, but pre-treatment with a V2 antagonist abolished the effect of Ang-(1–7) on P
f. Similarly, pre-treatment with A-779 inhibited AVPs effect on P
f. Forskolin-stimulated P
f was blocked both by A-779 and by the V2 antagonist. Finally, Ang-(1–7) increased cAMP levels in fresh IMCD cell suspensions whilst the forskolin-stimulated cAMP synthesis was decreased by A-779 and the V2 antagonist. These data provide evidence that Ang-(1–7) interacts via its receptor with the AVP V2 system through a mechanism involving adenylate-cyclase activation. 相似文献