全文获取类型
收费全文 | 6385篇 |
免费 | 524篇 |
国内免费 | 19篇 |
专业分类
耳鼻咽喉 | 23篇 |
儿科学 | 132篇 |
妇产科学 | 126篇 |
基础医学 | 1041篇 |
口腔科学 | 38篇 |
临床医学 | 690篇 |
内科学 | 1329篇 |
皮肤病学 | 125篇 |
神经病学 | 717篇 |
特种医学 | 138篇 |
外科学 | 576篇 |
综合类 | 33篇 |
一般理论 | 3篇 |
预防医学 | 611篇 |
眼科学 | 91篇 |
药学 | 582篇 |
中国医学 | 11篇 |
肿瘤学 | 662篇 |
出版年
2023年 | 55篇 |
2022年 | 86篇 |
2021年 | 206篇 |
2020年 | 104篇 |
2019年 | 191篇 |
2018年 | 200篇 |
2017年 | 128篇 |
2016年 | 169篇 |
2015年 | 183篇 |
2014年 | 251篇 |
2013年 | 345篇 |
2012年 | 534篇 |
2011年 | 499篇 |
2010年 | 285篇 |
2009年 | 213篇 |
2008年 | 424篇 |
2007年 | 454篇 |
2006年 | 399篇 |
2005年 | 363篇 |
2004年 | 369篇 |
2003年 | 335篇 |
2002年 | 286篇 |
2001年 | 53篇 |
2000年 | 36篇 |
1999年 | 64篇 |
1998年 | 64篇 |
1997年 | 45篇 |
1996年 | 44篇 |
1995年 | 32篇 |
1994年 | 21篇 |
1993年 | 22篇 |
1992年 | 24篇 |
1991年 | 15篇 |
1990年 | 26篇 |
1989年 | 25篇 |
1988年 | 21篇 |
1987年 | 19篇 |
1986年 | 12篇 |
1985年 | 27篇 |
1984年 | 12篇 |
1983年 | 15篇 |
1982年 | 17篇 |
1981年 | 18篇 |
1980年 | 10篇 |
1979年 | 16篇 |
1978年 | 15篇 |
1973年 | 9篇 |
1970年 | 8篇 |
1969年 | 11篇 |
1965年 | 8篇 |
排序方式: 共有6928条查询结果,搜索用时 125 毫秒
31.
32.
Properties of simian virus 40 mutants lacking the Asp4-Glu-Asp stretch at the carboxyl-terminus of large T antigen 总被引:1,自引:0,他引:1
The biological activity carried by the carboxy-terminal domain of SV40 large T antigen has been investigated by isolating mutants deleted for a stretch of six acidic residues which by analogy with polyoma middle T antigen might be essential for the activity of the protein. We have constructed an "in-phase" deletion of 37 residues that includes the complete acid residues cluster. In order to parallel the polyoma hr-t mutants genotype, the deletion was introduced in virus strains either competent or defective for the small t antigen. We conclude from these experiments that the deletion of this unusual sequence does not affect per se any of the known biological properties of the virus. 相似文献
33.
Detection and characterization of hepatitis C virus RNA in seminal plasma and spermatozoon fractions of semen from patients attempting medically assisted conception 下载免费PDF全文
34.
Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson's disease 总被引:5,自引:0,他引:5
Simon DK Lin MT Zheng L Liu GJ Ahn CH Kim LM Mauck WM Twu F Beal MF Johns DR 《Neurobiology of aging》2004,25(1):71-81
Oxidative damage to mitochondrial DNA (mtDNA) increases with age in the brain and can induce G:C to T:A and T:A to G:C point mutations. Though rare at any particular site, multiple somatic mtDNA mutations induced by oxidative damage or by other mechanisms may accumulate with age in the brain and thus could play a role in aging and neurodegenerative diseases. However, no prior study has quantified the total burden of mtDNA point mutation subtypes in the brain. Using a highly sensitive cloning and sequencing strategy, we find that the aggregate levels of G:C to T:A and T:A to G:C transversions and of all point mutations increase with age in the frontal cortex (FCtx). In the substantia nigra (SN), the aggregate levels of point mutations in young controls are similar to the levels in the SN or FCtx of elderly subjects. Extrapolation from our data suggests an average of 2.7 (FCtx) to 3.2 (SN) somatic point mutations per mitochondrial genome in elderly subjects. There were no significant differences between Parkinson's disease (PD) patients and age-matched controls in somatic mutation levels. These results indicate that individually rare mtDNA point mutations reach a high aggregate burden in FCtx and SN of elderly subjects. 相似文献
35.
Ndung'u T Gaseitsiwe S Sepako E Doualla-Bell F Peter T Kim S Thior I Novitsky VA Essex M 《Clinical and diagnostic laboratory immunology》2005,12(9):1020-1028
Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Botswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Botswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs. 相似文献
36.
Coindre JM Hostein I Maire G Derré J Guillou L Leroux A Ghnassia JP Collin F Pedeutour F Aurias A 《The Journal of pathology》2004,203(3):822-830
Inflammatory malignant fibrous histiocytoma (inflammatory MFH) is a very rare tumour that occurs most often in the retroperitoneum. So far, it has been considered to be a special subtype of MFH. As it is now widely accepted that most retroperitoneal pleomorphic MFHs are dedifferentiated liposarcomas, the present study compared histological features, genomic profile (CGH analysis), and MDM2 and CDK4 status (immunohistochemistry, FISH, and quantitative PCR) in inflammatory MFHs from 12 patients and dedifferentiated liposarcomas that had an inflammatory MFH component from eight patients. Metaphase cytogenetic and FISH analyses were also performed on one inflammatory MFH. Histological review showed areas of well-differentiated liposarcoma in nine inflammatory MFHs. CGH analysis showed 12q13-15 amplification or gain in six of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Immunohistochemistry showed positivity of tumour cells for MDM2 in every tumour in both groups and for CDK4 in ten and seven inflammatory MFHs and dedifferentiated liposarcomas, respectively. Metaphase cytogenetic and FISH analysis performed on one inflammatory MFH showed the presence of a supernumerary large marker chromosome and ring chromosome with high-level amplification of both MDM2 and CDK4 genes. FISH analysis on paraffin wax-embedded sections showed amplifications of MDM2 and CDK4 in seven of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas. 相似文献
37.
Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone 总被引:3,自引:0,他引:3 下载免费PDF全文
Pirnay JP De Vos D Cochez C Bilocq F Pirson J Struelens M Duinslaeger L Cornelis P Zizi M Vanderkelen A 《Journal of clinical microbiology》2003,41(3):1192-1202
To study the epidemiology of Pseudomonas aeruginosa colonization in a 32-bed burn wound center (BWC), 321 clinical and 45 environmental P. aeruginosa isolates were collected by prospective surveillance culture over a 1-year period and analyzed by serotyping, drug susceptibility testing, and amplified fragment length polymorphism (AFLP) analysis. Among 441 patients treated at the center, 70 (16%) were colonized with P. aeruginosa, including 12 (17%) patients who were colonized on admission and 58 (83%) patients who acquired the organism during their stay. Of the 48 distinct AFLP genotypes found, 21 were found exclusively in the environment, 15 were isolated from individual patients only, and 12 were responsible for the colonization of 57 patients, of which 2 were also isolated from the environment, but secondary to patient carriage. Polyclonal P. aeruginosa colonization with strains of two to four genotypes, often with different antibiotic susceptibility patterns, was observed in 19 patients (27%). Two predominant genotypes were responsible for recurrent outbreaks and the colonization of 42 patients (60% of all colonized patients). The strain with one of those genotypes appeared to be endemic to the BWC and developed multidrug resistance (MDR) at the end of the study period, whereas the strain with the other genotype was antibiotic susceptible but resistant to silver sulfadiazine (SSD(r)). The MDR strain was found at a higher frequency in sputum samples than the SSD(r) strain, which showed a higher prevalence in burn wound samples, suggesting that anatomic habitat selection was associated with adaptive resistance to antimicrobial drugs. Repeated and thorough surveys of the hospital environment failed to detect a primary reservoir for any of those genotypes. Cross-acquisition, resulting from insufficient compliance with infection control measures, was the major route of colonization in our BWC. In addition to the AFLP pattern and serotype, analysis of the nucleotide sequences of three (lipo)protein genes (oprI, oprL, and oprD) and the pyoverdine type revealed that all predominant strains except the SSD(r) strain belonged to recently identified clonal complexes. These successful clones are widespread in nature and therefore predominate in the patient population, in whom variants accumulate drug resistance mechanisms that allow their transmission and persistence in the BWC. 相似文献
38.
Marion Imbert-Bouteille Frédéric Tran Mau Them Julien Thevenon Thomas Guignard Vincent Gatinois Jean-Baptiste Riviere Anne Boland Vincent Meyer Jean-François Deleuze Elodie Sanchez Florence Apparailly David Geneviève Marjolaine Willems 《European journal of medical genetics》2019,62(3):161-166
Alazami syndrome (AS) (MIM# 615071) is an autosomal recessive microcephalic primordial dwarfism (PD) with recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported. Here we describe two consanguineous Algerian sisters with Alazami PD due to LARP7 homozygous pathogenic variants detected by whole exome sequencing. By comparing these two additional cases with those previously reported, we strengthen the key features of AS: severe growth restriction, severe intellectual disability and some distinguishing facial features such as broad nose, malar hypoplasia, wide mouth, full lips and abnormally set teeth. We also report significant new findings enabling further delineation of this syndrome: disproportionately mild microcephaly, stereotypic hand wringing and severe anxiety, thickened skin over the hands and feet, and skeletal, eye and heart malformations. From previous reviews, we summarize the main etiologies of PD according to the involved mechanisms and cellular pathways, highlighting their clinical core features. 相似文献
39.
Florence P. Haseltine Vincent A. Lynch Daniel L. Van Dyke W. Roy Breg Uta Francke John M. Opitz 《American journal of medical genetics. Part A》1982,13(2):115-123
Cells from three patients with early gonadal failure and a balanced reciprocal translocation involving the long arm of the X chromosome and an autosome were studied. Fibroblasts from a patient with a similar balanced reciprocal translocation but normal reproductive capabilities were also studied. Two of the four patients were found to have serologically detectable H-Y antigen on their cells. Since H-Y antigen has been found on the cells of other patients with X chromosome abnormalities but without a Y chromosome, it is thought that the X chromosome plays a role in the regulation of H-Y antigen expression. This study suggests that the long arm of the X chromosome may be involved but the location of a regulatory gene cannot be identified in these studies. These cases do not permit us to implicate H-Y antigen as a cause of gonadal dysgenesis and early gonadal failure in females who have structurally abnormal X chromosomes. 相似文献
40.
Evidence for the Presence of Insulin-Dependent Diabetes-Associated Alleles on the Distal Part of Mouse Chromosome 6 下载免费PDF全文
Evie Melanitou Florence Joly Mark Lathrop Christian Boitard Philip Avner 《Genome research》1998,8(6):608-620
Type 1 diabetes (IDDM) is a complex disorder with multifactorial and polygenic etiology. A genome-wide screen performed in a BC1 cohort of a cross between the nonobese diabetic (NOD) mouse with the diabetes-resistant feral strain PWK detected a major locus contributing to diabetes development on the distal part of chromosome 6. Unlike the majority of other Idd loci identified in intraspecific crosses, susceptibility is associated with the presence of the PWK allele. Genetic linkage analysis of congenic lines segregating PWK chromosome 6 segments in a NOD background confirmed the presence of the Idd locus within this region. The genetic interval defined by analysis of congenic animals showed a peak of significant linkage (P=0.0005) centered on an ~9-cM region lying between D6Mit11 and D6Mit25 genetic markers within distal mouse chromosome 6. 相似文献