全文获取类型
收费全文 | 881篇 |
免费 | 60篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 51篇 |
妇产科学 | 41篇 |
基础医学 | 146篇 |
口腔科学 | 31篇 |
临床医学 | 113篇 |
内科学 | 186篇 |
皮肤病学 | 34篇 |
神经病学 | 29篇 |
特种医学 | 131篇 |
外科学 | 56篇 |
综合类 | 37篇 |
预防医学 | 33篇 |
眼科学 | 5篇 |
药学 | 39篇 |
中国医学 | 2篇 |
肿瘤学 | 17篇 |
出版年
2023年 | 5篇 |
2021年 | 16篇 |
2020年 | 14篇 |
2019年 | 22篇 |
2018年 | 14篇 |
2017年 | 20篇 |
2016年 | 20篇 |
2015年 | 27篇 |
2014年 | 33篇 |
2013年 | 34篇 |
2012年 | 18篇 |
2011年 | 15篇 |
2010年 | 50篇 |
2009年 | 39篇 |
2008年 | 19篇 |
2007年 | 29篇 |
2006年 | 15篇 |
2005年 | 22篇 |
2004年 | 12篇 |
2003年 | 15篇 |
2002年 | 12篇 |
2001年 | 9篇 |
2000年 | 12篇 |
1999年 | 16篇 |
1998年 | 47篇 |
1997年 | 39篇 |
1996年 | 38篇 |
1995年 | 24篇 |
1994年 | 33篇 |
1993年 | 29篇 |
1992年 | 12篇 |
1991年 | 10篇 |
1990年 | 11篇 |
1989年 | 26篇 |
1988年 | 20篇 |
1987年 | 17篇 |
1986年 | 14篇 |
1985年 | 14篇 |
1984年 | 8篇 |
1983年 | 13篇 |
1982年 | 16篇 |
1981年 | 14篇 |
1980年 | 17篇 |
1979年 | 3篇 |
1978年 | 6篇 |
1977年 | 13篇 |
1976年 | 9篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1956年 | 3篇 |
排序方式: 共有956条查询结果,搜索用时 15 毫秒
41.
Occupational allergy and asthma is a serious adverse health outcome affecting seafood-processing workers. Allergic reactions are directed to two major seafood groups: fish and shellfish, with the latter group comprising crustaceans and molluscs. Several allergenic proteins have been identified in these different groups, but few have been characterised on a molecular level. Parvalbumin appears to be the major fish allergen, while tropomyosin the major crustacean allergen. Other IgE-binding proteins have also been identified in molluscs and other seafood-associated agents (e.g. Anisakis sp), although their molecular nature has not been characterised. Aerosolised allergens can be identified and quantified using immunological and chemical approaches, detecting levels as low as 10 ng/m3. This contemporary review discusses interesting and recent findings in the area of occupational seafood allergy including high-risk occupations, environmental risk factors for airborne exposures, major and minor allergens implicated and innovative approaches in diagnosing and managing occupational allergy and asthma associated with seafood processing. 相似文献
42.
Danielle Carpenter Carmen Taype Jon Goulding Mike Levin Brian Eley Suzanne Anderson Marie-Anne Shaw John AL Armour 《BMC medical genetics》2014,15(1):1-8
Background
22q11.2 deletion syndrome (22q11.2DS) is a common microdeletion syndrome, which occurs in approximately 1:4000 births. Familial autosomal dominant recurrence of the syndrome is detected in about 8-28% of the cases. Aim of this study is to evaluate the intergenerational and intrafamilial phenotypic variability in a cohort of familial cases carrying a 22q11.2 deletion.Methods
Thirty-two 22q11.2DS subjects among 26 families were enrolled.Results
Second generation subjects showed a significantly higher number of features than their transmitting parents (212 vs 129, P?=?0.0015). Congenital heart defect, calcium-phosphorus metabolism abnormalities, developmental and speech delay were more represented in the second generation (P?<?0.05). Ocular disorders were more frequent in the parent group. No significant difference was observed for the other clinical variables. Intrafamilial phenotypic heterogeneity was identified in the pedigrees. In 23/32 families, a higher number of features were found in individuals from the second generation and a more severe phenotype was observed in almost all of them, indicating the worsening of the phenotype over generations. Both genetic and epigenetic mechanisms may be involved in the phenotypic variability.Conclusions
Second generation subjects showed a more complex phenotype in comparison to those from the first generation. Both ascertainment bias related to patient selection or to the low rate of reproductive fitness of adults with a more severe phenotype, and several not well defined molecular mechanism, could explain intergenerational and intrafamilial phenotypic variability in this syndrome. 相似文献43.
Hermine A van Duyvenvoorde Julian C Lui Sarina G Kant Wilma Oostdijk Antoinet CJ Gijsbers Mari?tte JV Hoffer Marcel Karperien Marie JE Walenkamp Cees Noordam Paul G Voorhoeve Verónica Mericq Alberto M Pereira Hedi L Claahsen-van de Grinten Sandy A van Gool Martijn H Breuning Monique Losekoot Jeffrey Baron Claudia AL Ruivenkamp Jan M Wit 《European journal of human genetics : EJHG》2014,22(5):602-609
Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes. 相似文献
44.
Background: Exposure to antigens of the fish parasite Anisakis is associated with the development of protein contact dermatitis in seafood‐processing workers. Understanding the basic mechanisms controlling allergic sensitization through the skin is critical for designing therapies that will prevent the progression of allergic disease. Objective: To investigate the roles of interleukin (IL)‐4, IL‐13 and the IL‐4Rα in both local skin pathology and systemic sensitization following epicutaneous exposure to Anisakis proteins. Methods: BALB/c wild‐type (WT) mice and mice deficient in IL‐4, IL‐13 or IL‐4 and IL‐13, as well as mice with cell‐specific impairment of IL‐4Rα expression, were sensitized to Anisakis antigen by repeated epicutaneous application of Anisakis extract. Following this sensitization, skin pathology was recorded and systemic responses were investigated. Intravenous challenge with Anisakis extract was performed to test for the development of biologically relevant systemic sensitization. Results: In WT mice, epicutaneous sensitization with Anisakis larval antigens induced localized inflammation, epidermal hyperplasia, production of TH2 cytokines, antigen‐specific IgE and IgG1. Intravenous challenge of sensitized mice resulted in anaphylactic shock. Interestingly, IL‐13 deficient mice failed to develop epidermal hyperplasia and inflammation, whilst anaphylaxis was reduced only in strains deficient either in IL‐4 only, or deficient in IL‐4 and IL‐13 concurrently, as well as in mice deficient in IL‐4Rα or with impaired IL‐4Rα expression on CD4+ T cells. Conclusions: Interleukin‐13 plays a central role in protein contact dermatitis associated with repeated epicutaneous exposure to Anisakis extract, whereas IL‐4 drives systemic sensitization and resultant anaphylactic shock. 相似文献
45.
Edward?J?HolloxEmail author Jane?Davies Uta?Griesenbach Juliana?Burgess Eric?WFW?Alton John?AL?Armour 《Journal of negative results in biomedicine》2005,4(1):9
Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in
lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in
copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic
fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with
CF. No significant association was found. 相似文献
46.
Debelenko LV; Brambilla E; Agarwal SK; Swalwell JI; Kester MB; Lubensky IA; Zhuang Z; Guru SC; Manickam P; Olufemi SE; Chandrasekharappa SC; Crabtree JS; Kim YS; Heppner C; Burns AL; Spiegel AM; Marx SJ; Liotta LA; Collins FS; Travis WD; Emmert-Buck MR 《Human molecular genetics》1997,6(13):2285-2290
Lung carcinoids occur sporadically and rarely in association with multiple
endocrine neoplasia type 1 (MEN1). There are no well defined genetic
abnormalities known to occur in these tumors. We studied 11 sporadic lung
carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene
on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy
fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was
studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene
were inactivated. All four tumors showed the presence of a MEN1 gene
mutation and loss of the other allele. Observed mutations included a 1 bp
insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide
substitution affecting a donor splice site. Each mutation predicts
truncation or potentially complete loss of menin. The remaining seven
tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH.
The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a
complex germline MEN1 gene mutation. The data implicate the MEN1 gene in
the pathogenesis of sporadic lung carcinoids, representing the first
defined genetic alteration in these tumors.
相似文献
47.
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
48.
Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture 总被引:3,自引:1,他引:3
We have recently shown using dansyl-L-lysine exclusion studies that the
release of human chorionic gonadotrophin (HCG) in conjunction with L-
lactate dehydrogenase (LDH) from first trimester villi during organ culture
is symptomatic of syncytiotrophoblast degeneration. The purpose of this
study was to examine chorionic villi at the ultrastructural level in order
to determine events occurring during organ culture. The tissue was sampled
after 0, 24, 48 and 120 h in culture and processed for electron microscopy.
In addition to confirming the previously recorded syncytial degeneration,
the electron micrographs showed clearly the generation of a new
syncytiotrophoblast layer. The new layer, derived from differentiating
cytotrophoblast cells, was largely formed by 48 h and was maintained for at
least 120 h in culture. This study demonstrates a model which provides an
opportunity to study the differentiation of cytotrophoblast cells whilst
they retain their anatomical relationships within the villous structure.
相似文献
49.
50.
Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1) 总被引:10,自引:1,他引:10
Rousseau F; el Ghouzzi V; Delezoide AL; Legeai-Mallet L; Le Merrer M; Munnich A; Bonaventure J 《Human molecular genetics》1996,5(4):509-512
Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with
micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced
thoracic cavity. In the most common subtype (TD1), femurs are curved, while
in TD2, straight femurs are associated with cloverleaf skull. Mutations in
the fibroblast growth factor receptor 3 (FGFR3) gene were identified in
both subtypes. While TD2 was accounted for by a single recurrent mutation
in the tyrosine kinase 2 domain, TD1 resulted from either stop codon
mutations or missense mutations in the extracellular domain of the gene.
Here, we report the identification of FGFR3 mutations in 25/26 TD cases.
Two novel missense mutations (Y373C and G370C) were detected in 8/26 and
1/26 TD1 cases respectively. Both mutations created cysteine residues in
the juxta extramembrane domain of the receptor. Sixteen cases carried the
previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon
FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically
homogeneous condition and give additional support to the view that newly
created cysteine residues in the extracellular domain of the protein play a
key role in the severity of the disease.
相似文献