全文获取类型
收费全文 | 5513篇 |
免费 | 309篇 |
国内免费 | 34篇 |
专业分类
耳鼻咽喉 | 71篇 |
儿科学 | 138篇 |
妇产科学 | 162篇 |
基础医学 | 701篇 |
口腔科学 | 146篇 |
临床医学 | 375篇 |
内科学 | 1430篇 |
皮肤病学 | 110篇 |
神经病学 | 513篇 |
特种医学 | 143篇 |
外科学 | 917篇 |
综合类 | 31篇 |
预防医学 | 316篇 |
眼科学 | 81篇 |
药学 | 234篇 |
中国医学 | 15篇 |
肿瘤学 | 473篇 |
出版年
2023年 | 49篇 |
2022年 | 87篇 |
2021年 | 285篇 |
2020年 | 120篇 |
2019年 | 217篇 |
2018年 | 229篇 |
2017年 | 165篇 |
2016年 | 138篇 |
2015年 | 143篇 |
2014年 | 226篇 |
2013年 | 291篇 |
2012年 | 460篇 |
2011年 | 521篇 |
2010年 | 262篇 |
2009年 | 240篇 |
2008年 | 357篇 |
2007年 | 361篇 |
2006年 | 345篇 |
2005年 | 327篇 |
2004年 | 259篇 |
2003年 | 240篇 |
2002年 | 208篇 |
2001年 | 28篇 |
2000年 | 28篇 |
1999年 | 40篇 |
1998年 | 42篇 |
1997年 | 28篇 |
1996年 | 15篇 |
1995年 | 20篇 |
1994年 | 14篇 |
1993年 | 18篇 |
1992年 | 13篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1981年 | 9篇 |
1980年 | 3篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1974年 | 2篇 |
1947年 | 1篇 |
1944年 | 1篇 |
1942年 | 1篇 |
1936年 | 1篇 |
1920年 | 1篇 |
排序方式: 共有5856条查询结果,搜索用时 62 毫秒
31.
Gaforio JJ Ortega E Algarra I Serrano MJ Alvarez de Cienfuegos G 《Clinical and diagnostic laboratory immunology》2002,9(6):1282-1294
The participation of NK cells in the activation of splenic macrophages or in resistance to systemic candidiasis is still a matter of debate. We had previously reported that there is a correlation between natural killer cell activation and resistance to systemic candidiasis. In those experiments we had used tilorone to boost NK cell activity in mice. Here we show a mechanism elicited by tilorone in splenic macrophages which could explain their effect on mouse survival during acute disseminated Candida albicans infection. The results demonstrate that tilorone treatment elicits, by a direct effect, the production of proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-alpha], and IL-12) by splenic macrophages. In addition, it increases the capacity of splenic macrophages to phagocytize C. albicans through activation of NK cells. We also demonstrate that the presence of NK cells is essential for maintaining a basal level of phagocytic activity, which characterizes splenic macrophages of na?ve control mice. The results demonstrate that it is possible to identify two phenotypically and functionally peculiar cell populations among splenic macrophages: (i). cells of the "stimulator/secretor phenotype," which show high levels of major histocompatibility complex (MHC) class II surface expression, are poorly phagocytic, and synthesize the proinflammatory cytokines IL-6, TNF-alpha, and IL-12, and (ii). cells of the "phagocytic phenotype," which express low levels of MHC class II molecules, are highly phagocytic, and do not secrete proinflammatory cytokines. 相似文献
32.
Ignacio Algarra Matías Pérez Jose Juan Gaforio Fernando Gasca Federico Garrido 《Clinical & experimental metastasis》1994,12(1):31-36
The role of different tilorone analogs in the abrogation of the metastatic spread of H-2 positive and H-2 negative tumor clones was studied. Pre-treatment of BALB/c mice with RMI 10,874DA compound completely abolished lung colonization of an H-2 negative (GR9.B9) MCA-induced fibrosarcoma clone in an experimental metastasis assay. This effect was also evident when clones were treated with other tilorone analogs (R11,567DA or R11,513DA). Other H-2 positive and H-2 negative chemically induced fibrosarcoma clones were also tested. The effect was not due to direct toxicity of the tilorone analog on tumor cells, but instead was dependent on NK cells; this was suggested by the finding that treatment of mice with anti-asialo GM1 abrogated the effect of the tilorone analog (RMI 10,874DA compound). Interestingly, the inhibition of lung colonization after intravenous injection was again observed regardless of the H-2 phenotype of the tumor clones, and H-2+ and H-2– clones were similarly inhibited.In vitro assays of NK sensitivity of tumor clones showed that lysis varied depending on the H-2 phenotype of tumor clones, indicating an absence of correlation betweenin vivo andin vitro results. 相似文献
33.
Susana Camacho Maria Del Valle Ostos José Ignacio Llorente Ana Sanz Manuel García Alberto Domezain Ramón Carmona 《Anatomical record (Hoboken, N.J. : 2007)》2007,290(9):1178-1189
Ampullary organs of Acipenser naccarii sturgeons were examined by optical and electronic microscopy (transmission electron microscopy and scanning electron microscopy) from hatching until 1 month later when the juvenile phase is completely established. It was observed that, when A. naccarii begins to feed actively, the ultrastructural characteristics of ampullary organs already correspond to those of adult animals. These organs may, therefore, be functional and, together with taste buds, facilitate food search after exhaustion of yolk sac food reserves. Mature ampullary organs of A. naccarii are formed by an ampulla that communicates with the exterior by means of a short channel. These ampullae correspond to the sensory portion of these receptors and are formed by two cell types: receptor cells and support cells. Receptor cells present a kinocilium on their free surface and establish ribbon synapses with axon nerve endings that arise from the underlying conjunctive tissue. Support cells enclose receptor cells, bear stereocilia and occasional cilia, and are of a secretory nature. The mucus associated with ampullary organs mainly comprises neutral mucopolysaccharides, whereas mucopolysaccharides are usually acid in other fish groups. Anat Rec, 290:1178–1189, 2007. © 2007 Wiley‐Liss, Inc. 相似文献
34.
Moying Tang Yumai Pires Marcela Schultz Ignacio Duarte Marcela Gallegos Ignacio I Wistuba 《Diagnostic molecular pathology》2003,12(3):151-159
Despite well-established histopathological features and the development of immunostaining of human neoplasms, there are a number of cases in which surgical pathologists cannot assure the origin of synchronous and metachronous tumors. In many cases, the classification of these lesions as either two separate primary tumors or as a single primary tumor with a metastasis has significant implications with respect to patient prognosis and recommendations for therapy. To establish the origin of tumors, we assessed tumor cell clonality using PCR-based microsatellite analysis on microdissected archival tissues for loss of heterozygosity (LOH) and microsatellite instability (MSI) in a series of 19 paired synchronous and metachronous tumors from several organs. As a control group, 15 autopsy cases with an unequivocally recognizable primary tumor and associated metastases were also examined. Based on LOH and MSI findings, and using a panel of 4 to 12 (median 7) microsatellite markers, we were able to establish the clonal pattern of microsatellite changes in 17 out of 19 (89%) biopsy cases and thus determine if they were either double primary tumors (41%) or metastases (59%). Of interest, identical or similar pattern of microsatellite abnormalities were detected in 15 primary tumors and corresponding metastasis from autopsies. Our results indicate that microsatellite analysis for LOH and MSI, as an expression of clonality, provides a useful tool to distinguish double primary neoplasms and metastases in synchronous and metachronous tumors. 相似文献
35.
The V599E BRAF mutation is uncommon in biliary tract cancers. 总被引:1,自引:0,他引:1
David Goldenberg Eli Rosenbaum Pedram Argani Ignacio I Wistuba David Sidransky Paul J Thuluvath Manuel Hidalgo Joseph Califano Anirban Maitra 《Modern pathology》2004,17(11):1386-1391
Activating point mutations of the BRAF oncogene have been identified in several solid tumors, most commonly in cutaneous melanomas and papillary carcinomas of the thyroid. A specific point mutation--V599E--accounts for the overwhelming majority of these mutational events. We explored the frequency of the V599E BRAF mutation in biliary tract cancers. In all, 62 archival biliary tract cancers, including 15 gallbladder cancers, 15 extrahepatic, and 10 intrahepatic cholangiocarcinomas from the United States, and 22 gallbladder carcinomas from Chile were analyzed for the V599E mutation of the BRAF gene using three distinct methods: direct sequencing, a primer extension method (Mutector assay), and the highly sensitive quantitative Gap Ligase Chain Reaction. The common V599E mutation was not identified in any of the 62 biliary cancer samples using these three methods of detection. The V599E somatic mutation of the BRAF gene is absent in biliary tract cancers, at least in the two geographic populations (United States and Chile) examined. Activation of the RAS/RAF/MAP kinase pathway in biliary tract cancers is likely to be secondary to oncogenic RAS mutations, or due to mutations of the BRAF gene at nucleotide positions not explored in the current study. 相似文献
36.
Azaiez H Chamberlin GP Fischer SM Welp CL Prasad SD Taggart RT del Castillo I Van Camp G Smith RJ 《Human mutation》2004,24(4):305-311
Genetic testing was completed on 1,294 persons with deafness referred to the Molecular Otolaryngology Research Laboratories to establish a diagnosis of DFNB1. Exon 2 of GJB2 was screened for coding sequence allele variants by denaturing high-performance liquid chromatography (DHPLC) complemented by bidirectional sequencing. If two deafness-causing mutations of GJB2 (encoding Connexin 26) were identified, further screening was not performed. If only a single deafness-causing mutation was identified, we screened for the g.1777179_2085947del (hereafter called del(GJB6-D13S1830); GenBank NT_024524.13) and mutations in the noncoding region of GJB2. Phenotype-genotype correlations were evaluated by categorizing mutations as either protein truncating or nontruncating. A total of 205 persons carried two GJB2 exon 2 mutations and were diagnosed as having DFNB1; 100 persons carried only a single deafness-causing allele variant of exon 2. A total of 37 of these persons were c.35delG carriers, and 51 carried other allele variants of GJB2. Persons diagnosed with DFNB1 segregating two truncating/nonsense mutations had a more severe phenotype than persons carrying two missense mutations, with mean hearing impairments being 88 and 37%, respectively (P < 0.05). The number of deaf c.35delG carriers was greater than expected when compared to the c.35delG carrier frequency in normal-hearing controls (P < 0.05), suggesting the existence of at least one other mutation outside the GJB2 coding region that does not complement GJB2 deafness-causing allele variants. 相似文献
37.
38.
39.
García-Samaniego J Soriano V Miró JM Romero JD Bruguera M Castilla J Esteban JI Gonźlez J Lissen E Moreno A Moreno S Moreno-Otero R Ortega E Quereda C Rodríguez M Sánchez-Tapias JM;Spanish Hepatitis-HIV Consensus Panel 《HIV clinical trials》2002,3(2):99-114
Co-infection by human immunodeficiency virus and hepatitis B and C viruses is quite common because they share similar routes of transmission. The introduction of highly active antiretroviral therapy has significantly improved the life expectancy of HIV-infected patients in the last few years. However, chronic viral hepatitis represents an emerging cause of morbidity and mortality in this population, either as a result of end-stage liver disease or as a consequence of hepatotoxicity induced by antiretroviral drugs. The main goal of the Consensus Conference was to establish specific recommendations for the management of chronic viral hepatitis B and C in HIV-infected patients. The role of orthotopic liver transplantation for co-infected individuals with end-stage liver disease was also assessed. 相似文献
40.
Ignacio Prieto Charles Tease Nieves Pezzi José M. Buesa Sagrario Ortega Leonor Kremer Alicia Martínez Carlos Martínez-A Maj A. Hultén José L. Barbero 《Chromosome research》2004,12(3):197-213
Cohesins are chromosomal proteins that form complexes involved in the maintenance of sister chromatid cohesion during division of somatic and germ cells. Three meiosis-specific cohesin subunits have been reported in mammals, REC8, STAG3 and SMC1 beta; their expression in mouse spermatocytes has also been described. Here we studied the localization of different meiotic and mitotic cohesin components during prophase I in human and murine female germ cells. In normal and atretic human fetal oocytes, from leptotene to diplotene stages, REC8 and STAG3 colocalize in fibers. In murine oocytes, SMC1beta, SMC3 and STAG3 are localized along fibers that correspond first to the chromosome axis and then to the synaptonemal complex in pachytene. Mitotic cohesin subunit RAD21 is also found in fibers that decorate the SC during prophase I in mouse oocytes, suggesting a role for this cohesin in mammalian sister chromatid cohesion in female meiosis. We observed that, unlike human oocytes, murine synaptonemal complex protein SYCP3 localizes to nucleoli throughout prophase I stages, and centromeres cluster in discrete locations from leptotene to dictyate. At difference from meiosis in male mice, the cohesin axis is progressively lost during the first week after birth in females with a parallel destruction of the axial elements at dictyate arrest, demonstrating sexual dimorphism in sister chromatid cohesion in meiosis. 相似文献