全文获取类型
收费全文 | 124178篇 |
免费 | 8448篇 |
国内免费 | 449篇 |
专业分类
耳鼻咽喉 | 1630篇 |
儿科学 | 3294篇 |
妇产科学 | 2070篇 |
基础医学 | 15963篇 |
口腔科学 | 2368篇 |
临床医学 | 12524篇 |
内科学 | 26276篇 |
皮肤病学 | 1914篇 |
神经病学 | 11946篇 |
特种医学 | 4269篇 |
外国民族医学 | 4篇 |
外科学 | 17994篇 |
综合类 | 1881篇 |
现状与发展 | 1篇 |
一般理论 | 167篇 |
预防医学 | 11091篇 |
眼科学 | 2908篇 |
药学 | 8692篇 |
2篇 | |
中国医学 | 172篇 |
肿瘤学 | 7909篇 |
出版年
2023年 | 470篇 |
2022年 | 696篇 |
2021年 | 2067篇 |
2020年 | 1228篇 |
2019年 | 2012篇 |
2018年 | 2318篇 |
2017年 | 1787篇 |
2016年 | 1958篇 |
2015年 | 2412篇 |
2014年 | 3438篇 |
2013年 | 5330篇 |
2012年 | 7759篇 |
2011年 | 8281篇 |
2010年 | 4687篇 |
2009年 | 4510篇 |
2008年 | 7968篇 |
2007年 | 8515篇 |
2006年 | 8349篇 |
2005年 | 8638篇 |
2004年 | 8168篇 |
2003年 | 7998篇 |
2002年 | 7571篇 |
2001年 | 1181篇 |
2000年 | 927篇 |
1999年 | 1229篇 |
1998年 | 1703篇 |
1997年 | 1424篇 |
1996年 | 1162篇 |
1995年 | 1147篇 |
1994年 | 942篇 |
1993年 | 960篇 |
1992年 | 754篇 |
1991年 | 704篇 |
1990年 | 670篇 |
1989年 | 624篇 |
1988年 | 576篇 |
1987年 | 543篇 |
1986年 | 545篇 |
1985年 | 662篇 |
1984年 | 831篇 |
1983年 | 830篇 |
1982年 | 1162篇 |
1981年 | 1052篇 |
1980年 | 951篇 |
1979年 | 464篇 |
1978年 | 576篇 |
1977年 | 547篇 |
1976年 | 449篇 |
1975年 | 408篇 |
1974年 | 367篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
941.
Najmabadi H Nishimura C Kahrizi K Riazalhosseini Y Malekpour M Daneshi A Farhadi M Mohseni M Mahdieh N Ebrahimi A Bazazzadegan N Naghavi A Avenarius M Arzhangi S Smith RJ 《American journal of medical genetics. Part A》2005,(2):132-137
Hereditary hearing loss (HHL) is a very common disorder. When inherited in an autosomal recessive manner, it typically presents as an isolated finding. Interestingly and unexpectedly, in spite of extreme heterogeneity, mutations in one gene, GJB2, are the most common cause of congenital severe-to-profound deafness in many different populations. In this study, we assessed the contributions made by GJB2 mutations and chromosome 13 g.1777179_2085947del (the deletion more commonly known as del (GJB6-D13S1830) that includes a portion of GJB6 and is hereafter called Delta(GJB6-D13S1830)) to the autosomal recessive non-syndromic deafness (ARNSD) genetic load in Iran. Probands from 664 different nuclear families were investigated. GJB2-related deafness was found in 111 families (16.7%). The carrier frequency of the 35delG mutation showed a geographic variation that is supported by studies in neighboring countries. Delta(GJB6-D13S1830) was not found. Our prevalence data for GJB2-related deafness reveal a geographic pattern that mirrors the south-to-north European gradient and supports a founder effect in southeastern Europe. 相似文献
942.
Infection of the reproductive tract and eggs with Salmonella enterica serovar pullorum in the chicken is associated with suppression of cellular immunity at sexual maturity 下载免费PDF全文
Wigley P Hulme SD Powers C Beal RK Berchieri A Smith A Barrow P 《Infection and immunity》2005,73(5):2986-2990
Salmonella enterica serovar Pullorum causes persistent infections in laying hens. Splenic macrophages are the main site of persistence. At sexual maturity, numbers of bacteria increase and spread to the reproductive tract, which may result in vertical transmission to eggs or chicks. In this study we demonstrate that both male and female chickens may develop a carrier state following infection but that the increases in bacterial numbers and spread to the reproductive tract are phenomena restricted to hens, indicating that such changes are likely to be related to the onset of egg laying. The immunological responses during the carrier state and through the onset of laying in hens were determined. These indicate that chickens produce both humoral and T-cell responses to infection, but at the onset of laying both the T-cell response to Salmonella and nonspecific responses to mitogenic stimulation fall sharply in both infected and noninfected birds. The fall in T-cell responsiveness coincided with the increase in numbers of Salmonella serovar Pullorum and its spread to the reproductive tract. Three weeks after the onset of egg laying, T-cell responsiveness began to increase and bacterial numbers declined. Specific antibody levels changed little at the onset of laying but increased following the rise in bacterial numbers in a manner reminiscent of a secondary antibody response to rechallenge. These findings indicate that a nonspecific suppression of cellular responses occurs at the onset of laying and plays a major role the ability of Salmonella serovar Pullorum to infect the reproductive tract, leading to transmission to eggs. The loss of T-cell activity at the point of laying also has implications for Salmonella enterica serovar Enteritidis infection and transmission to eggs, along with its control by vaccination offering a "window of opportunity" in which infection may occur. 相似文献
943.
Joyce PR Porter RJ Mulder RT Luty SE McKenzie JM Miller AL Kennedy MA 《Psychological medicine》2005,35(4):511-517
BACKGROUND: Although diurnal variation of mood is a widely recognized symptom of depression, the clinical, neurobiological and psychopharmacological significance of this symptom has not previously been reported. METHOD: A total of 195 depressed out-patients underwent a detailed clinical and neurobiological assessment, and were then randomized to treatment with either fluoxetine or nortriptyline. RESULTS: Of the 195 depressed patients, 62 had a pattern of reversed diurnal variation (i.e. worse in the evening). Those with reversed diurnal variation had a poorer response to a serotonergic anti-depressant, were less likely to have bipolar II disorder, had a higher tryptophan: large neutral amino acid ratio and had different allele frequencies of the polymorphisms in the promoter region of the serotonin transporter. CONCLUSIONS: These findings raise the possibility of serotonergic influence on diurnal variation, and that the symptom of reversed diurnal variation is of relevance to antidepressant prescribing. 相似文献
944.
Persistence of multiple variants of rabies virus in wild Chiroptera and Carnivora presents a continuing challenge to medical, veterinary and wildlife management professionals. Oral rabies vaccination (ORV) targeting specific Carnivora species has emerged as an integral adjunct to conventional rabies control strategies to protect humans and domestic animals. ORV has been applied with progress toward eliminating rabies in red foxes (Vulpes vulpes) in western Europe and southern Ontario, Canada. More recently since 1995, coordinated ORV was implemented among eastern states in the U.S.A. to prevent spread of raccoon (Procyon lotor) rabies and to contain and eliminate variants of rabies virus in the gray fox (Urocyon cinereoargenteus) and coyote (Canis latrans) in Texas. In this paper, we describe the current cooperative ORV program in the U.S.A. and discuss the importance of coordination of surveillance and rabies control programs in Canada, Mexico and the U.S.A. Specifically, several priorities have been identified for these programs to succeed, which include additional oral vaccines, improved baits to reach target species, optimized ORV strategies, effective communication and legal strategies to limit translocation across ORV barriers, and access to sufficient long-term funding. These key priorities must be addressed to ensure that ORV has the optimal chance of achieving long range programmatic goals of eliminating specific variants of rabies virus in North American terrestrial carnivores. 相似文献
945.
Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects,increased cancer susceptibility,and male and female sterility 总被引:12,自引:0,他引:12 下载免费PDF全文
Wei K Clark AB Wong E Kane MF Mazur DJ Parris T Kolas NK Russell R Hou H Kneitz B Yang G Kunkel TA Kolodner RD Cohen PE Edelmann W 《Genes & development》2003,17(5):603-614
Exonuclease 1 (Exo1) is a 5'-3' exonuclease that interacts with MutS and MutL homologs and has been implicated in the excision step of DNA mismatch repair. To investigate the role of Exo1 in mammalian mismatch repair and assess its importance for tumorigenesis and meiosis, we generated an Exo1 mutant mouse line. Analysis of Exo1(-/-) cells for mismatch repair activity in vitro showed that Exo1 is required for the repair of base:base and single-base insertion/deletion mismatches in both 5' and 3' nick-directed repair. The repair defect in Exo1(-/-) cells also caused elevated microsatellite instability at a mononucleotide repeat marker and a significant increase in mutation rate at the Hprt locus. Exo1(-/-) animals displayed reduced survival and increased susceptibility to the development of lymphomas. In addition, Exo1(-/-) male and female mice were sterile because of a meiotic defect. Meiosis in Exo1(-/-) animals proceeded through prophase I; however, the chromosomes exhibited dynamic loss of chiasmata during metaphase I, resulting in meiotic failure and apoptosis. Our results show that mammalian Exo1 functions in mutation avoidance and is essential for male and female meiosis. 相似文献
946.
Ikeda S Cunningham LA Boggess D Hawes N Hobson CD Sundberg JP Naggert JK Smith RS Nishina PM 《Human molecular genetics》2003,12(9):1029-1037
Corneal disease is the most common cause of bilateral blindness in the world. Visual loss in this condition is often due to changes in morphology and function of the corneal epithelial surface. Corneal disease-1 (corn1) and corn1(2J) are spontaneous mouse mutants that develop irregular thickening of the corneal epithelium, similar to that observed in human corneal surface disease. These autosomal-recessive mutations cause an increase in the rate of proliferation of the corneal epithelial cells. Here, we report that the phenotypes in both mutants are caused by mutations within the destrin gene (also known as actin-depolymerizing factor). By positional cloning, we identified a deletion encompassing the entire coding sequence of the destrin gene in corn1 mice, and a point mutation (Pro106Ser) in the coding sequence of destrin in corn1(2J) mice. In situ analysis showed that destrin is highly expressed in the corneal epithelium. Consistent with the cellular roles for destrin, an essential regulator of actin filament turnover that acts by severing and enhancing depolymerization of actin filament, we observed that the corn1 mutations increased the content of filamentous actin in corneal epithelial cells. Our results suggest an in vivo connection between remodeling of the actin cytoskeleton and the control of cell proliferation, and a new pathway through which an aberrant actin cytoskeleton can cause epithelial hyperproliferation. 相似文献
947.
Identification and characterization of a new variant of Shiga toxin 1 in Escherichia coli ONT:H19 of bovine origin 下载免费PDF全文
Bürk C Dietrich R Açar G Moravek M Bülte M Märtlbauer E 《Journal of clinical microbiology》2003,41(5):2106-2112
A new variant of Shiga toxin 1 (Stx1), designated Stx1d, which deviates considerably more than any other known variant from Stx1 encoded by phage 933J, was identified in an Escherichia coli strain, ONT:H19, isolated from bovine feces. The complete stx(1) gene of this strain was amplified and sequenced. Nucleotide sequence homology with stx(1) from phage 933J was only 91%, resulting in the substitution of 20 amino acids in the A subunit and 7 amino acids in the B subunit of the protein. Cell culture supernatant of this strain, which was negative for stx(2) by PCR testing, was cytotoxic to Vero cells and gave positive results in two commercial enzyme-linked immunosorbent assays for Stx. PCR primers were constructed for the specific detection of the new variant. The findings of this study suggest that Stx1 is not as conserved as thought before and that there might be more variants which cannot be detected by commonly used PCR methods. 相似文献
948.
Traditional approaches to generating tissue-engineered arteries in vitro rely on expansion of cells in culture to seed appropriate scaffolds. In most envisioned applications, small autologous blood vessels would be harvested and used as a source for these cells. We propose that small autologous arteries, not the cells derived from them, may be an attractive starting point for engineered arteries. This approach capitalizes on the ability of intact arteries to grow and remodel in response to chronic changes in their mechanical environment. Carotid arteries from juvenile (approximately 30-kg) pigs were stretched longitudinally in an ex vivo perfusion system over 9 days. This resulted in a 40% increase in artery length at physiological longitudinal stress and a 20 +/- 3% increase when unstressed. Control arteries were perfused for 9 days ex vivo at their physiological loaded length. Control and elongated arteries displayed native appearance (macroscopic and histological), excellent viability (cellularity and mitochondrial activity), normal vasoactivity, and similar mechanical properties (ultimate stress and ultimate strain) as compared with freshly harvested arteries. Growth, as opposed to just redistribution of existing mass, contributed to elongation as evidenced by an increase in artery weight. Results on elongation of arteries from neonatal and adolescent pigs are also presented and discussed. 相似文献
949.
Sawyer EJ Hanby AM Poulsom R Jeffery R Gillett CE Ellis IO Ellis P Tomlinson IP 《The Journal of pathology》2003,200(5):627-632
The aim of this study was to assess the expression of IGF-I and IGF-II in phyllodes tumours and fibroadenomas and to see if there is any correlation between nuclear beta-catenin expression and IGF-I and IGF-II expression in these tumours. In a previous study, it has been shown that Wnt signalling is important in the pathogenesis of phyllodes tumours of the breast. Epithelial Wnt5a overexpression and stromal Wnt2 overexpression were associated with abnormal, nuclear localization of beta-catenin in the stromal cells of these tumours. However, not all tumours with beta-catenin accumulation showed Wnt overexpression. One other possible cause of beta-catenin accumulation is overexpression of insulin-like growth factors (IGFs), as both IGF-I and IGF-II have been shown to stabilize beta-catenin. In this study, 30 fibroadenomas of the breast were assessed for beta-catenin expression using immunohistochemistry and the results were compared with previous data from 119 phyllodes tumours. In situ hybridization was used to assess IGF-I and IGF-II expression in 23 phyllodes tumours and 16 fibroadenomas. Nineteen phyllodes tumours (83%) showed widespread overexpression of IGF-II and 5/23 (22%) showed widespread overexpression of IGF-I. IGF-I expression correlated with nuclear beta-catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF-I expression. There was a degree of nuclear beta-catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear beta-catenin staining correlated with IGF-I overexpression. Extensive IGF-II overexpression was also found in the majority of fibroadenomas (12/16). These results support the hypothesis that IGF-I and IGF-II overexpression may be important in the pathogenesis of fibroepithelial neoplasms of the breast and that IGF-I overexpression is likely to be contributing to the nuclear beta-catenin localization observed in the tumours. 相似文献
950.
Mode of delivery and risk of developing allergic disease 总被引:3,自引:0,他引:3
McKeever TM Lewis SA Smith C Hubbard R 《The Journal of allergy and clinical immunology》2002,109(5):800-802
The aim of this study was to quantify the relationship between mode of delivery and subsequent incidence of allergic disease. The analysis is based on data derived from a birth cohort of 24,690 children who contributed data to the West Midlands General Practice Research Database. We found no convincing evidence to suggest that babies born by caesarean, forceps, or breech delivery had an increased risk of developing allergic disease. 相似文献