全文获取类型
收费全文 | 10166篇 |
免费 | 688篇 |
国内免费 | 333篇 |
专业分类
耳鼻咽喉 | 115篇 |
儿科学 | 279篇 |
妇产科学 | 273篇 |
基础医学 | 2040篇 |
口腔科学 | 90篇 |
临床医学 | 717篇 |
内科学 | 1649篇 |
皮肤病学 | 116篇 |
神经病学 | 809篇 |
特种医学 | 239篇 |
外科学 | 744篇 |
综合类 | 1058篇 |
预防医学 | 1172篇 |
眼科学 | 92篇 |
药学 | 806篇 |
7篇 | |
中国医学 | 184篇 |
肿瘤学 | 797篇 |
出版年
2023年 | 148篇 |
2022年 | 360篇 |
2021年 | 387篇 |
2020年 | 410篇 |
2019年 | 330篇 |
2018年 | 353篇 |
2017年 | 342篇 |
2016年 | 332篇 |
2015年 | 431篇 |
2014年 | 708篇 |
2013年 | 728篇 |
2012年 | 541篇 |
2011年 | 715篇 |
2010年 | 508篇 |
2009年 | 583篇 |
2008年 | 587篇 |
2007年 | 532篇 |
2006年 | 508篇 |
2005年 | 394篇 |
2004年 | 332篇 |
2003年 | 286篇 |
2002年 | 185篇 |
2001年 | 188篇 |
2000年 | 145篇 |
1999年 | 143篇 |
1998年 | 104篇 |
1997年 | 103篇 |
1996年 | 77篇 |
1995年 | 96篇 |
1994年 | 72篇 |
1993年 | 61篇 |
1992年 | 56篇 |
1991年 | 51篇 |
1990年 | 40篇 |
1989年 | 26篇 |
1988年 | 24篇 |
1987年 | 24篇 |
1986年 | 26篇 |
1985年 | 41篇 |
1984年 | 34篇 |
1983年 | 18篇 |
1982年 | 26篇 |
1981年 | 23篇 |
1980年 | 21篇 |
1979年 | 20篇 |
1978年 | 18篇 |
1977年 | 7篇 |
1976年 | 8篇 |
1975年 | 10篇 |
1974年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 12 毫秒
51.
产前筛查和基因多态性位点在唐氏综合征产前诊断中的应用 总被引:6,自引:3,他引:6
目的 在建立可靠的产前筛查方法的同时,采用快速,简便,准确的产前诊断方法,防止唐氏综合征(DS)患儿的出生,方法 采用酶联免疫方法测定妊娠14-20w孕妇血清甲胎蛋白(AFP)和绒毛膜促性腺激素β亚基(β-HCG)浓度,结合孕妇年龄,孕周和体重,用计算机软件进行分析,得到每位孕妇所怀胎儿DS风险系数,对筛查出胎儿唐氏综合征高风险孕妇,再利用21号染色体上的6个多态性位点对其作产前基因诊断。结果 经产前筛查,在395例孕妇中发现10例胎儿唐氏综合征高风险孕妇,其中1例产前基因诊断为胎儿唐氏综合征,与染色体核型分析结果相符。结论 产前筛查结合基因多态性在唐氏综合征产前诊断中具有很好的应用价值。 相似文献
52.
Paul M. Kaye Cara Coburn Maria McCrossan Stephen M. Beverley 《European journal of immunology》1993,23(9):2311-2319
Processing of antigen for recognition by class II-restricted CD4+ T cells occurs within acidic compartments of the antigen-presenting cell. The exact nature of this compartment has yet to be precisely defined, however, but may vary depending upon the cell type studied and the antigen used. The acidic compartments of macrophages are also responsible for the degradation of ingested micro-organisms and play host to others which are adapted to an intracellular existance. To determine whether the phagolysosome (PL) formed in activated macrophages after ingestion of Leishmania parasites is also a site for entry of antigen into the class II presentation pathway, we have used the approach of genetic transformation. Hence, Leishmania were transfected with the genes for the protein antigens ovalbumin (OVA) and β-galactosidase (β-gal) and after infection were able to deliver these antigens specifically into the PL. Delivery of antigen to this site resulted in the ability of infected macrophages to present these antigens to antigen-specific CD4+ T cells. After taking into account the absolute levels of antigen uptake by macrophages, a 4-h processing period for OVA delivered by this or a soluble route led to equivalent levels of T cell activation. Unlike macrophages pulsed with soluble OVA, those with PL-targeted OVA still retained the ability to stimulate T cells after a 24-h processing period. This enhanced lifespan of antigen in macrophages corresponded to the kinetics of degradation of the parasite, suggesting slow release of antigen into the processing pathway. β-gal presentation from the PL was tenfold less efficient under the same conditions. In addition to providing the first information on antigen processing in a protozoan PL, these studies highlight the usefulness of genetically transformed parasites for these types of studies. 相似文献
53.
Joanne Young Barbara Leggett Corinne Gustafson Michael Ward Jeffrey Searle Lesley Thomas Ron Buttenshaw Georgia Chenevix-Trench 《Human mutation》1993,2(5):351-354
Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non-polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley-Liss, Inc. 相似文献
54.
目的探讨ABCB4基因突变合并巨细胞病毒(CMV)感染致婴儿胆汁淤积症(IC)患儿的临床特征、基因检测结果和诊治方案。 方法选择2019年8月3日,于中山大学附属第七医院就诊并确诊为ABCB4基因突变合并CMV感染致IC的1例婴儿(女性,生后9个月)为研究对象。回顾性分析其临床病例资料,包括临床特征、实验室检查结果及基因检测结果。同时,检索国内外数据库中ABCB4基因突变所致IC患儿的相关文献,并进行文献复习。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。 结果本例IC患儿在本院诊治结果如下。①病史采集:系G2P2,足月顺产,外观无异常,否认新生儿黄疸病史,生后2个月龄时出现皮肤及巩膜呈暗绿色,伴反复呕奶,当地医院治疗并诊断为胆汁淤积性肝病、CMV感染和泌尿系统感染,抗病毒治疗2周后好转出院。出院时,其血清总胆汁酸(sTBA)为152.8 μmol/L,CMV-DNA<4×102 copies/mL,口服熊去氧胆酸胶囊10 mg/(kg·d)治疗后,皮肤暗绿色逐渐消退,大、小便正常。出院后定期监测肝功能,sTBA、γ-谷氨酰转肽酶(GGT)仍然较正常值增高。②实验室检查:血清CMV免疫球蛋白(Ig)G抗体呈阳性、CMV IgM抗体呈阴性,CMV-DNA<55×102 copies/mL。基因检测结果:患儿及其父亲均携带ABCB4基因杂合变异。治疗结果:经口服熊去氧胆酸胶囊10 mg/(kg·d)及谷胱甘肽片0.1 g/次× 3次/d治疗后,对患儿定期复查sTBA、GGT。随访到18个月龄时,其各项指标逐渐恢复正常范围。③文献复习结果:共计检索到8篇国内外报道的因ABCB4基因突变引起IC相关文献,纳入14例IC患儿,均被诊断为进行性家族性肝内胆汁淤积3型(PFIC3),伴肝大,sTBA、GGT水平升高等。14例IC患儿中,共检测到ABCB4基因突变位点20个。其中,9例IC患儿接受熊去氧胆酸治疗,7例随访结果显示临床症状及实验室检查指标有所好转。 结论携带ABCB4基因突变,可引起IC。对于sTBA升高、肝酶异常的病因不明确、治疗效果不佳IC患儿,建议完善基因检测进一步排查ABCB4基因突变所致胆汁淤积症。 相似文献
55.
目的:为了解广西壮族人群D1S80位点群体遗传资料,方法,使用扩增片段长度多态性(Amp-Flp)和PCR结合聚丙烯酰胺凝电脉及银染技术,对300名文本地区壮族无关个体D1S80位点多态性分析,结果,观察到23个等位基因,74个基因型,杂合度,非交排除率,个体识别力及多态信息含量分别为0.824,0.763,0.968,0.875,其基因频率分布符合Hardy-weinberg定律,对5个家系相关个体分析符合孟德尔定律,结认,该方法具有快速,简便,特异性强,灵敏度高特点。 相似文献
56.
57.
Kyriakos Chatzopoulos Sotiris Sotiriou Andrea R. Collins Panagiotis Kartsidis Alessandra C. Schmitt Xianfeng Chen Khashayarsha Khazaie Michael L. Hinni Colleen A. Ramsower Matthew A. Zarka Samir H. Patel Joaquin J. Garcia 《Head and neck pathology》2021,15(2):509
The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R2 = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users. 相似文献
58.
在介导体内外基因转移方面,脂质体已显示出许多优于病毒载体的特征.然而,有关脂质体介导造血细胞基因转移的报道很少.本文描述了脂质体介导双标志基因(Neo~R和Lac Z)在体外共转移进入人及小鼠原代造血细胞的研究.基因转移的效率通过X-gal染色及观察集落的形成来评价.结果显示,在存在G418的体系中,转导细胞能够存活并形成集落,而未转导细胞则不能存活.同时,转导阳性细胞能够被X-gal染成蓝色.其蓝染阳性细胞率在人及小鼠造血细胞于G418选择前分别为13.33± 2.68%和16.28± 2.95%.经G418选择启分别达到46.06±3.47%及43.45±4.1%,显著高于筛选前(P<0.01).提示,利用脂质体这一简单、安全的转导策略在原代造血细胞可获得高效的基因转移及稳定的表达.同时,共转导双标志基因进入造血细胞可用作高集转导阳性细胞.这一结论对于临床进一步探讨造血重建的生物学特征、追踪白血病的复发机制以及利用造血细胞作为靶细胞进行基因治疗的研究提供了实验依据. 相似文献
59.
A prospective study of biochemical changes after vertical banded gastroplasty for morbid obesity, in 94 patients (10 males
and 84 females, ages ranging from 18 to 59 years) has been carried out. Liver function tests and electrolyte estimations were
performed preoperatively, during hospitalisation for surgery, at 6 weeks and at 6 months postoperatively, and demonstrated
no significant changes in liver function in these patients 6 months after surgery. The study concludes that there is no increase
in the risk of liver damage or electrolyte disturbance after vertical gastroplasty, but that there may be subtle hepatic changes
present as gall bladder disease developed in 18 patients postoperation (19%). 相似文献
60.