全文获取类型
收费全文 | 17227篇 |
免费 | 1485篇 |
国内免费 | 377篇 |
专业分类
耳鼻咽喉 | 84篇 |
儿科学 | 369篇 |
妇产科学 | 352篇 |
基础医学 | 3262篇 |
口腔科学 | 361篇 |
临床医学 | 1227篇 |
内科学 | 2790篇 |
皮肤病学 | 551篇 |
神经病学 | 1305篇 |
特种医学 | 588篇 |
外国民族医学 | 2篇 |
外科学 | 1665篇 |
综合类 | 1560篇 |
现状与发展 | 3篇 |
预防医学 | 673篇 |
眼科学 | 233篇 |
药学 | 2166篇 |
3篇 | |
中国医学 | 617篇 |
肿瘤学 | 1278篇 |
出版年
2023年 | 261篇 |
2022年 | 442篇 |
2021年 | 611篇 |
2020年 | 606篇 |
2019年 | 859篇 |
2018年 | 758篇 |
2017年 | 696篇 |
2016年 | 698篇 |
2015年 | 738篇 |
2014年 | 1112篇 |
2013年 | 1221篇 |
2012年 | 1061篇 |
2011年 | 1198篇 |
2010年 | 870篇 |
2009年 | 769篇 |
2008年 | 704篇 |
2007年 | 583篇 |
2006年 | 457篇 |
2005年 | 391篇 |
2004年 | 379篇 |
2003年 | 355篇 |
2002年 | 276篇 |
2001年 | 240篇 |
2000年 | 192篇 |
1999年 | 160篇 |
1998年 | 148篇 |
1997年 | 143篇 |
1996年 | 107篇 |
1995年 | 124篇 |
1994年 | 92篇 |
1993年 | 92篇 |
1992年 | 94篇 |
1991年 | 86篇 |
1990年 | 84篇 |
1989年 | 51篇 |
1988年 | 61篇 |
1987年 | 56篇 |
1985年 | 218篇 |
1984年 | 305篇 |
1983年 | 236篇 |
1982年 | 208篇 |
1981年 | 212篇 |
1980年 | 180篇 |
1979年 | 179篇 |
1978年 | 126篇 |
1977年 | 108篇 |
1976年 | 137篇 |
1975年 | 109篇 |
1974年 | 100篇 |
1973年 | 86篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
81.
Melanoma-associated peptides recognized by cytolytic T lymphocytes (CTL) in the context of several histocompatibility leukocyte antigens (HLA) are required for the development of specific immunotherapies. Using a transient transfection assay into COS-7 cells, we identified the gp100/pMel17 melanosomal protein as the shared antigen recognized by three independent CD8+ CTL clones in HLA-A*6801-restricted fashion. This finding was confirmed by the correlation between lack of gp100/pMel17 protein in a number of HLA-A*6801-positive melanomas and their resistance to lysis/cytokine production by the specific effectors. The gp100/pMel17 antigenic epitope was identified based on recognition of subfragments and on a computer-based prediction algorithm. Among a panel of gp100/pMel17-derived synthetic peptides only the 10-mer HTMEVTVYHR (gp100/pMel17182-191) induced tumor necrosis factor (TNF) release by CTL clones when pulsed on suitable target cells whereas both the 10-mer and the shorter 9-mer gp100/pMel17183-191 sensitized the same antigen-pulsed cells to lysis. In conclusion, the identification of the HTMEVTVYHR peptide will extend to HLA-A*6801 melanoma patients the possibility to exploit gp100/pMel17 melanosomal protein for experimental and clinical studies. 相似文献
82.
目的检测广东地区正常人群和鼻咽癌患者中细胞色素P450酶系CYP2F1基因的多态性,并分析该基因遗传多态性与鼻咽癌易感性的关联。方法采用直接测序法检测40例鼻咽癌患者全血标本中CYP2F1基因全部10个外显子的多态性变化。对于等位基因频率较高的多态性位点,进一步采用错配聚合酶链反应.限制性片段长度多态性检测368例鼻咽癌患者和344名正常对照人群中该位点的等位基因频率。结果在40例鼻咽癌样本中,共检测到CYP2F1基因的35个单核苷酸多态性。其中,10个单核甘酸引起编码的氨基酸改变,1个移码突变,15~16bp之间插入C引起移码突变(15-16ins C),该等位基因频率为25%。但病例-对照分析却未能显示该位点突变与鼻咽癌易感的相关性(P〉0.05)。结论中国广东人的CYP2F1基因遗传多态性位点较多,但暂未发现与鼻咽癌的易感性关联的单一多态位点,多个多态性位点或不同基因多态性位点的协同互补作用可能才是鼻咽癌发生发展的关键影响因素。 相似文献
83.
Immunohistochemical analysis of centromere protein F expression in buccal and gingival squamous cell carcinoma 总被引:4,自引:0,他引:4
Centromere protein F (CENP-F) expression (localization and characteristics) in relation to tumor clinicopathological parameters was immunohistochemically examined and evaluated in 47 archival biopsy specimens of buccal and gingival squamous cell carcinomas (SCC). Centromere protein F expression was detected in 79% of the samples. An increase in the labeling index (LI) with WHO grading was obtained ( P < 0.05). Correlations were obtained between the CENP-F LI and tumor size ( P < 0.05). Immunoelectron microscopy showed CENP-F nuclear staining as punctate or fine dots. The present study shows that CENP-F expression and detection of a more specific cell subpopulation presents a theoretical advantage for the analysis of the precise cell cycle of G2 to M cells, compared to Ki-67. 相似文献
84.
We report three possibly disease-causing point mutations in one of the inner-ear-specific genes, KIAA1199. We identified an R187C mutation in one family, an R187H mutation in two unrelated families, and an H783Y mutation in one sporadic case of nonsyndromic hearing loss. In situ hybridization indicated that the murine homolog of KIAA1199 mRNA is expressed specifically in Deiters cells in the organ of Corti at postnatal day zero (Pn) P0 before the onset of hearing, but expression in those cells disappears by day P7. The signal of KIAA1199 was also observed in fibrocytes of the spiral ligament and the spiral limbus through to P21, when the murine cochlea matures. Thus, the gene product may be involved in uptake of potassium ions or trophic factors with a particular role in auditory development. Although the R187C and R187H mutations did not appear to affect subcellular localization of the gene product in vitro, the H783Y mutation did present an unusual cytoplasmic distribution pattern that could underlie the molecular mechanism of hearing impairment. Our data bring attention to a novel candidate for hearing loss and indicate that screening of mutations in inner-ear-specific genes is likely to be an efficient approach to finding genetic elements responsible for deafness.Nucleotide sequence data reported herein are available in the DDBJ/EMBL/GenBank databases; for details, see the electronic eatabase section of this article. 相似文献
85.
Postnatal development of somatostatin-containing neurons in the visual cortex of normal and dark-reared rats 总被引:1,自引:0,他引:1
G. C. Papadopoulos M. E. Cavanagh J. Antonopoulos H. Michaloudi J. G. Parnavelas 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1993,92(3):473-478
Summary The distribution of somatostatin (SRIF)-immunoreactive neurons in the visual cortical areas 17, 18 and 18a of Wistar rats from birth to adulthood was followed in both normal and dark-reared animals. The SRIF neurons show difference in distribution amongst the three cortical areas studied as early as the first postnatal week. Area 17 was distinguished by fewer SRIF cells in the upper layers (I–III), which results in a lower overall density. The SRIF neurons in all areas appeared to increase in numbers up to about 3 weeks and then decline dramatically to adult levels, which were 14–19% of the peak levels. Although this decline was still obvious, it moderated to 25–31% in dark-reared animals. The greatest effect was seen in area 18 where, at 60 days of age, there were twice as many SRIF cells in darkreared as in normal controls. It is suggested that, under conditions of dark rearing, the overall pattern of development of SRIF neurons, being uninfluenced by extrinsic factors, reveals the cells' genetic potential. 相似文献
86.
William F. Benedict Ashutosh Banerjee Corey Mark A. Linn Murphree 《Cancer Genetics and Cytogenetics》1983,10(4):311-333
The karotypic patterns of 15 retinoblastomas were examined. Five tumors were found to have two distinct stem lines and, therefore, the chromosomal patterns of 20 tumor cell lines are reported. Three nonrandom chromosomal changes, namely, a loss of a chromosome #13, the presence of an i(6p), or a trisomy of 1q were observed. The potential importance of these chromosomal changes in tumor development is discussed, particularly the loss of a chromosome #13 or the gain of an i(6p). At least one of the three chromosomal changes was found in 75% of the tumor lines analyzed. 相似文献
87.
目的 :观察棘球蚴囊内容物攻击兔所至肺功能和形态的损害。建立囊型包虫肺栓塞的动物模型。方法 :取囊型包虫内容物 ,分离出囊砂 ,与囊液配成 5 %的悬浊液。 2 1只家兔 ,分 3组 :Ⅰ :生理盐水组 ,Ⅱ :澄清囊液组 ,Ⅲ :囊砂悬浊液组。每只家兔都置入股动脉导管及股静脉导管。依照上述分组按 2mL/kg体重分别自静脉导管注射生理盐水、澄清囊液或含囊砂的悬浊液。于注射后 ( 5、30、6 0min)动态监测MAP、血气指标及血清血管活性物质(ET - 1、TXB2 、6 -keto -PGF1α)水平的变化。指标测定后 ,行肺部ECT检查。最后取出动物肺脏行光镜病检。结果 :Ⅲ组和Ⅱ组在注射后均出现MAP、血气指标的明显降低 (P <0 .0 5 )和血清TXB2 、6 -keto -PGF1α的升高 (P <0 .0 5 ) ,尤以Ⅲ组最明显 (P <0 .0 5 )。各组动物血清ET - 1水平在注射前后无明显变化 (P >0 .0 1)。ECT显示Ⅲ组动物肺部放射性缺损 ,Ⅱ组动物肺部放射性减弱。Ⅲ组肺脏病检见头节广泛栓塞于肺小动脉、微小动脉中 ,肺脏呈“急性呼吸窘迫综合症样”改变。Ⅱ组肺组织出现淤血、水肿及炎细胞浸润。结论 :Ⅲ组动物基本能够模拟出囊型包虫病肺栓塞的临床表现。囊液中有形成分在肺损害中起着重要的作用。TXB2 、6 -keto -PGF1α参与了肺损伤病理过程。 相似文献
88.
Megan E. Rech John M. McCarthy Chun‐An Chen Jane C. Edmond Veeral S. Shah Daniëlle G. M. Bosch Gerard T. Berry Linford Williams Suneeta Madan‐Khetarpal Dmitriy Niyazov Charles Shaw‐Smith Erin M. Kovar Philip J. Lupo Christian P. Schaaf 《American journal of medical genetics. Part A》2020,182(6):1426-1437
Bosch–Boonstra–Schaaf Optic Atrophy Syndrome (BBSOAS) is an autosomal dominant neurodevelopmental disorder caused by loss‐of‐function variants in NR2F1 and characterized by visual impairment, developmental delay, and intellectual disability. Here we report 18 new cases, provide additional clinical information for 9 previously reported individuals, and review an additional 27 published cases to present a total of 54 patients. Among these are 22 individuals with point mutations or in‐frame deletions in the DNA‐binding domain (DBD), and 32 individuals with other types of variants including whole‐gene deletions, nonsense and frameshift variants, and point mutations outside the DBD. We corroborate previously described clinical characteristics including developmental delay, intellectual disability, autism spectrum disorder diagnoses/features thereof, cognitive/behavioral anomalies, hypotonia, feeding difficulties, abnormal brain MRI findings, and seizures. We also confirm a vision phenotype that includes optic nerve hypoplasia, optic atrophy, and cortical visual impairment. Additionally, we expand the vision phenotype to include alacrima and manifest latent nystagmus (fusional maldevelopment), and we broaden the behavioral phenotypic spectrum to include a love of music, an unusually good long‐term memory, sleep difficulties, a high pain tolerance, and touch sensitivity. Furthermore, we provide additional evidence for genotype–phenotype correlations, specifically supporting a more severe phenotype associated with DBD variants. 相似文献
89.
90.
A novel C202F mutation in the connexin26 gene (GJB2) associated with autosomal dominant isolated hearing loss 下载免费PDF全文
Morlé L Bozon M Alloisio N Latour P Vandenberghe A Plauchu H Collet L Edery P Godet J Lina-Granade G 《Journal of medical genetics》2000,37(5):368-370
Mutations in the GJB2 gene encoding connexin26 (CX26) account for up to 50% of cases of autosomal recessive hearing loss. In contrast, only one GJB2 mutation has been reported to date in an autosomal dominant form of isolated prelingual hearing loss. We report here a novel heterozygous 605G→T mutation in GJB2 in all affected members of a large family with late childhood onset of autosomal dominant isolated hearing loss. The resulting C202F substitution, which lies in the fourth (M4) transmembrane domain of CX26, may impair connexin oligomerisation. Finally, our study suggests that GJB2 should be screened for heterozygous mutations in patients with autosomal dominant isolated hearing impairment, whatever the severity of the disease.
Keywords: C202F mutation; connexin26 gene (GJB2); autosomal dominant hearing loss 相似文献
Keywords: C202F mutation; connexin26 gene (GJB2); autosomal dominant hearing loss 相似文献