全文获取类型
收费全文 | 1659篇 |
免费 | 112篇 |
国内免费 | 25篇 |
专业分类
儿科学 | 146篇 |
妇产科学 | 19篇 |
基础医学 | 160篇 |
口腔科学 | 68篇 |
临床医学 | 157篇 |
内科学 | 386篇 |
皮肤病学 | 38篇 |
神经病学 | 40篇 |
特种医学 | 332篇 |
外科学 | 136篇 |
综合类 | 22篇 |
预防医学 | 61篇 |
眼科学 | 17篇 |
药学 | 110篇 |
1篇 | |
中国医学 | 1篇 |
肿瘤学 | 102篇 |
出版年
2021年 | 13篇 |
2020年 | 10篇 |
2019年 | 13篇 |
2018年 | 24篇 |
2017年 | 21篇 |
2016年 | 26篇 |
2015年 | 34篇 |
2014年 | 28篇 |
2013年 | 50篇 |
2012年 | 16篇 |
2011年 | 20篇 |
2010年 | 47篇 |
2009年 | 83篇 |
2008年 | 26篇 |
2007年 | 47篇 |
2006年 | 43篇 |
2005年 | 39篇 |
2004年 | 25篇 |
2003年 | 29篇 |
2002年 | 23篇 |
2001年 | 21篇 |
2000年 | 22篇 |
1999年 | 32篇 |
1998年 | 101篇 |
1997年 | 119篇 |
1996年 | 113篇 |
1995年 | 77篇 |
1994年 | 83篇 |
1993年 | 98篇 |
1992年 | 20篇 |
1991年 | 23篇 |
1990年 | 21篇 |
1989年 | 46篇 |
1988年 | 39篇 |
1987年 | 30篇 |
1986年 | 38篇 |
1985年 | 37篇 |
1984年 | 23篇 |
1983年 | 17篇 |
1982年 | 21篇 |
1981年 | 35篇 |
1980年 | 23篇 |
1979年 | 17篇 |
1978年 | 14篇 |
1977年 | 26篇 |
1976年 | 23篇 |
1975年 | 7篇 |
1969年 | 5篇 |
1967年 | 8篇 |
1966年 | 8篇 |
排序方式: 共有1796条查询结果,搜索用时 0 毫秒
61.
P Martínez‐Montero M Muoz‐Calero E Vallespín J Campistol L Martorell MJ Ruiz‐Falc A Santana R Pons A Dinopoulos C Sierra J Nevado J Molano 《Clinical genetics》2013,84(6):566-571
Pelizaeus–Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty‐eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation‐dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array‐CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array‐CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series. 相似文献
62.
Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP) 总被引:8,自引:0,他引:8
Rowe PS; Oudet CL; Francis F; Sinding C; Pannetier S; Econs MJ; Strom TM; Meitinger T; Garabedian M; David A; Macher MA; Questiaux E; Popowska E; Pronicka E; Read AP; Mokrzycki A; Glorieux FH; Drezner MK; Hanauer A; Lehrach H; Goulding JN; O'Riordan JL 《Human molecular genetics》1997,6(4):539-549
Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with
homologies to endopeptidases, on the X-chromosome), are responsible for
X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family
of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has
raised important questions regarding PEX function at the molecular level.
The aim of this study was to analyse 99 HYP families for PEX gene
mutations, and to correlate predicted changes in the protein structure with
Zn2+ metallopeptidase gene function. Primers flanking 22 characterised
exons were used to amplify DNA by PCR, and SSCP was then used to screen for
mutations. Deletions, insertions, nonsense mutations, stop codons and
splice mutations occurred in 83% of families screened for in all 22 exons,
and 51% of a separate set of families screened in 17 PEX gene exons.
Missense mutations in four regions of the gene were informative regarding
function, with one mutation in the Zn2+-binding site predicted to alter
substrate enzyme interaction and catalysis. Computer analysis of the
remaining mutations predicted changes in secondary structure,
N-glycosylation, protein phosphorylation and catalytic site molecular
structure. The wide range of mutations that align with regions required for
protease activity in NEP suggests that PEX also functions as a protease,
and may act by processing factor(s) involved in bone mineral metabolism.
相似文献
63.
Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1 总被引:10,自引:0,他引:10
Lemmens I; Van de Ven WJ; Kas K; Zhang CX; Giraud S; Wautot V; Buisson N; De Witte K; Salandre J; Lenoir G; Pugeat M; Calender A; Parente F; Quincey D; Gaudray P; De Wit MJ; Lips CJ; Hoppener JW; Khodaei S; Grant AL; Weber G; Kytola S; Teh BT; Farnebo F; Thakker RV 《Human molecular genetics》1997,6(7):1177-1183
64.
Spinal N-methyl-D-aspartate receptors and nociception-evoked release of primary afferent substance P 总被引:1,自引:0,他引:1
Dorsal horn N-methyl-D-aspartate (NMDA) receptors contribute significantly to spinal nociceptive processing through an effect postsynaptic to non-primary glutamatergic axons, and perhaps presynaptic to the primary afferent terminals. The present study sought to examine the regulatory effects of NMDA receptors on primary afferent release of substance P (SP), as measured by neurokinin 1 receptor (NK1r) internalization in the spinal dorsal horn of rats. The effects of intrathecal NMDA alone or in combination with D-serine (a glycine site agonist) were initially examined on basal levels of NK1r internalization. NMDA alone or when co-administered with D-serine failed to induce NK1r internalization, whereas activation of spinal TRPV1 receptors by capsaicin resulted in a notable NK1r internalization. To determine whether NMDA receptor activation could potentiate NK1r internalization or pain behavior induced by a peripheral noxious stimulus, intrathecal NMDA was given prior to an intraplantar injection of formalin. NMDA did not alter the formalin-induced NK1r internalization nor did it enhance the formalin paw flinching behavior. To further characterize the effects of presynaptic NMDA receptors, the NMDA antagonists DL-2-amino-5-phosphonopentanoic acid (AP-5) and MK-801 were intrathecally administered to assess their regulatory effects on formalin-induced NK1r internalization and pain behavior. AP-5 had no effect on formalin-induced NK1r internalization, whereas MK-801 produced only a modest reduction. Both antagonists, however, reduced the formalin paw flinching behavior. In subsequent in vitro experiments, perfusion of NMDA in spinal cord slice preparations did not evoke basal release of SP or calcitonin gene-related peptide (CGRP). Likewise, perfusion of NMDA did not enhance capsaicin-evoked release of the two peptides. These results suggest that presynaptic NMDA receptors in the spinal cord play little if any role on the primary afferent release of SP. 相似文献
65.
WHO生存质量评估简表的等价性评价 总被引:20,自引:0,他引:20
目的评价WHO生存质量评估简表(WHOQOL-BREF)在13个国家的等价性。方法采用多组验证性因子分析方法,对世界卫生组织生存质量研究小组提供的13个国家的数据进行分析,评价WHOQOL-BREF不同国家的等价性。结果各个国家的各个领域的Cronbachα系数均大于0·7,分布在0·7至0·88之间。除了英国和挪威之外,其它国家的社会关系领域的Cronbachα系数均大于0·65。采用根据世界卫生组织生存质量研究小组研制量表时构建的四因子模型对数据分别进行拟合,拟合优度指数(CFI)均大于0·8,其中德国、西班牙和美国的拟合优度指数大于0·9。多组验证性因子分析发现模型拟合尚可,CFI等于0·88,各个国家的因子负荷不全相等,因子负荷的轮廓相似。结论WHOQOL-BREF在13个国家具有相同的因子结构,且有等价性。 相似文献
66.
María Jesús Fernández Aceñero MD PhD Cristina Díaz del Arco CDdA MD Carme Dinarés CD MD PhD Tania Labiano TL MD Eva Tejerina ET MD PhD Mª José Bernabé MJ B MD Elena Forcen EF MD Melchor Saiz-Pardo MSP MD Pablo Pérez PP MD Maria D. Lozano MDL MD PhD 《Diagnostic cytopathology》2023,51(1):26-35
Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples. 相似文献
67.
Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. 总被引:4,自引:0,他引:4
Peng Hou Dingxie Liu Yuan Shan Shuiying Hu Kimberley Studeman Stephen Condouris Yangang Wang Ariel Trink Adel K El-Naggar Giovanni Tallini Vasily Vasko Mingzhao Xing 《Clinical cancer research》2007,13(4):1161-1170
PURPOSE: To investigate the overall occurrence and relationship of genetic alterations in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in thyroid tumors and explore the scope of this pathway as a therapeutic target for thyroid cancer. EXPERIMENTAL DESIGN: We examined collectively the major genetic alterations and their relationship in this pathway, including PIK3CA copy number gain and mutation, Ras mutation, and PTEN mutation, in a large series of primary thyroid tumors. RESULTS: Occurrence of any of these genetic alterations was found in 25 of 81 (31%) benign thyroid adenoma (BTA), 47 of 86 (55%) follicular thyroid cancer (FTC), 21 of 86 (24%) papillary thyroid cancer (PTC), and 29 of 50 (58%) anaplastic thyroid cancer (ATC), with FTC and ATC most frequently harboring these genetic alterations. PIK3CA copy gain was associated with increased PIK3CA protein expression. A mutual exclusivity among these genetic alterations was seen in BTA, FTC, and PTC, suggesting an independent role of each of them through the PI3K/Akt pathway in the tumorigenesis of the differentiated thyroid tumors. However, coexistence of these genetic alterations was increasingly seen with progression from differentiated tumor to undifferentiated ATC. Their coexistence with BRAF mutation was also frequent in PTC and ATC. CONCLUSIONS: The data provide strong genetic implication that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate. Progression of PTC to ATC may be facilitated by coexistence of PI3K/Akt pathway-related genetic alterations and BRAF mutation. The PI3K/Akt pathway may thus be a major therapeutic target in thyroid cancers. 相似文献
68.
Background
The Dutch Consumer Quality Index Hip Knee Questionnaire (CQI Hip Knee) was used to assess patients' experiences with and evaluations of quality of care after a total hip (THA) or total knee arthroplasty (TKA). The aim of this study is to evaluate the construct validity and internal consistency reliability of this new instrument and to assess its ability to measure differences in quality of care between hospitals. 相似文献69.
70.
DC Wilson MJ Cunningham MMcC Reid SS Johnston TF Fannin 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(1):84-85
A baby with unilateral cleft lip, midline cleft palate and hypertelorism developed meningitis in the first 48 h of life. Examination of the nasopharynx showed a soft tissue mass, which was confirmed as a basal encephalocele by computed tomography. There was also congenital hydrocephalus and the corpus callosum was absent. Surgical treatment included repair of the anterior basal skull defect, repair of the lip and palate, and ventriculo-peritoneal shunt. There is currently evidence of developmental delay and right-sided visual impairment due to Morning Glory syndrome. This case demonstrates that basal encephalocele should be considered in any baby with midline facial deformity who develops meningitis. 相似文献