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71.
Shaheen Alanee Sohela Shah Rajmohan Murali Rohini Rau-Murthy Kasmintan A. Schrader Kenneth Offit 《Familial cancer》2013,12(1):125-127
BRCA1 functions as a tumor suppressor gene and germline and somatic mutations in this gene have been shown to be associated with many types of cancer. We report the first tumor study of renal cell carcinoma in a carrier of the deleterious BRCA1 mutation-c.68_69delAG. 相似文献
72.
Martrat G Maxwell CM Tominaga E Porta-de-la-Riva M Bonifaci N Gómez-Baldó L Bogliolo M Lázaro C Blanco I Brunet J Aguilar H Fernández-Rodríguez J Seal S Renwick A Rahman N Kühl J Neveling K Schindler D Ramírez MJ Castellà M Hernández G;EMBRACE Easton DF Peock S Cook M Oliver CT Frost D Platte R Evans DG Lalloo F Eeles R Izatt L Chu C Davidson R Ong KR Cook J Douglas F Hodgson S Brewer C Morrison PJ Porteous M Peterlongo P Manoukian S Peissel B Zaffaroni D Roversi G Barile M Viel A Pasini B 《Breast cancer research : BCR》2011,13(2):R40
Introduction
Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens.Methods
Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk.Results
A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively.Conclusions
While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers. 相似文献73.
Pathological influence of obesity on renal structural changes in chronic kidney disease 总被引:1,自引:0,他引:1
Shigeko Kato Arifa Nazneen Yumiko Nakashima Mohammed S. Razzaque Tomoya Nishino Akira Furusu Noriaki Yorioka Takashi Taguchi 《Clinical and experimental nephrology》2009,13(4):332-340
Background Role of obesity in renal pathological and structural changes remains poorly investigated, and this study was designed to examine
the pathological effects of obesity on renal structural components in patients with chronic kidney diseases (CKD).
Methods The study subjects were obese (body mass index, BMI ≥ 25 kg/m2) patients with nonglomerulonephritis (non-GN, n = 26), IgA nephropathy (IgAN, n = 19), benign nephrosclerosis (BNS, n = 15), and thin basement membrane disease (TMD, n = 6), and 65 nonobese controls (n = 20, 20, 10, and 15, respectively). Patients were evaluated for glomerular lesions (mesangial proliferation and focal segmental/global
glomerulosclerosis), glomerular size, and thickness of glomerular basement membrane (GBM).
Results Urinary protein was higher in obese non-GN, IgAN, and BNS groups than in the respective controls. Focal segmental glomerulosclerosis
(FSGS) lesions were noted in all obesity groups. The glomeruli were larger in size in obese than in nonobese patients of the
non-GN and IgAN groups. The glomeruli of nonobese TMD and BNS patients were significantly larger in size than those of nonobese
non-GN patients. GBM were thicker in obese than in nonobese patients irrespective of types of glomerular diseases, but only
significantly so in non-GN and BNS groups.
Conclusion In non-GN, IgAN, and BNS, obesity worsens proteinuria and is associated with structural changes such as glomerulomegaly and
GBM thickening, similar to changes observed in obesity-related nephropathy. Obesity seems to worsen the renopathological state
in CKD. 相似文献
74.
BACKGROUND:
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, and the majority contain KIT or PDGFRA activating mutations. Fine‐needle aspiration biopsy (FNAB) is a valuable technique in the diagnosis of GIST and may allow for preoperative therapy with tyrosine kinase inhibitors (TKI). Because of the morphologic diversity of these tumors, routine diagnosis of GIST often relies on C‐Kit immunohistochemical staining in addition to morphologic findings. However, up to 15% of GISTs are C‐Kit negative. Antibodies with increased sensitivity and specificity for detection of C‐Kit–negative GIST cases may be of value, especially because some of these cases may also benefit from TKI therapy.METHODS:
Immunohistochemical staining for DOG‐1, C‐Kit (CD117) and protein kinase C theta (PKCθ) was performed on FNA cell‐block preparations representing 30 GISTs, 17 leiomyosarcomas, 16 melanomas, 16 schwannomas, 11 adenoid cystic carcinomas, and 8 leiomyomas.RESULTS:
DOG‐1 was found to have 100% sensitivity and 100% specificity in diagnosis of GIST. C‐Kit demonstrated 70% sensitivity and 76% specificity, and PKCθ showed 40% sensitivity and 86% specificity. When only spindle‐cell neoplasms were considered (adenoid cystic carcinomas excluded), the specificity of C‐Kit increased to 89%. Of interest, all C‐Kit–negative cases showed DOG‐1 positivity.CONCLUSIONS:
DOG‐1 was the most sensitive and specific of the 3 markers for the diagnosis of GIST in cell‐block preparations and may be of particular use in the diagnosis of C‐Kit–negative GIST. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society 相似文献75.
Dewji NN 《Journal of Alzheimer's disease : JAD》2006,10(2-3):277-290
Molecular genetic studies of familial Alzheimer's disease by 1995 had clearly implicated three proteins as critical to Alzheimer's disease (AD), the amyloid-beta protein precursor (AbetaPP) and the two homologous presenilins, PS-1 and PS-2. To account for the roles of these proteins in AD, we had proposed that as an early and critical step in the mechanisms that lead to AD, the PS on the surface of a brain cell engages in a specific receptor-ligand intercellular interaction with AbetaPP on the surface of a neighboring cell. This cell-cell interaction is required to trigger off a cascade of processes that lead to the production of amyloid-beta (Abeta) from AbetaPP, leading to AD. At about this time, however, many established AD researchers had obtained data that appeared to disagree with our proposed mechanism. Their immediate objections to our proposal were based on their conclusions that 1) The PS proteins were exclusively intracellular, and were not expressed at the cell surface, and 2) The topography of the PS proteins in intracellular membranes exhibits either 6 or 8-TM spanning domains, not 7. Here we discuss the evidence for the 6-TM, 7-TM, 8-TM and other models of PS topography and offer possibilities for the differences in interpretation of the various sets of data. We review the experimental demonstration of the cell-surface expression and the 7-TM structure of PS, the functional consequences of this structure, and the findings that PS-1 and PS-2 are members of the superfamily of 7-TM heterotrimeric G-protein coupled receptors (GPCRs). 相似文献
76.
Sohela MustariBelal HossainNurazzura Mohamad DiahSusmita Kar 《Asian Pacific journal of cancer prevention》2019,20(6):1613-1620
Each year, many countries from developed world publishes reports on early cancer detection; which is absolutelyabsent in most developing countries like Bangladesh.Very limited evidence is found on the role and acceptance of Paptest among the women of Bangladesh in determining cervical cancer. More research and updates are needed relating Paptest in early detection of cervical cancer. Thus the purpose of this study is set to assess the opinions of Bangladeshiurbanwomentowardsthe Pap test. A questionnaire-based survey of 400 Bangladeshi urban women was evaluated by on theirsocio-demographic characteristics, knowledgeand attitudes towards Pap testing. In general, the findings reveal thatrespondents havea good understanding of thepurpose of Pap test screening with 3.92 (Mean score). With 3.54 Meanscore,the respondents believed that Pap tests are recommended to women who are married and with 3.45 mean scorewomen believed that Pap tests arerecommended only to those who have children. Generally, respondents possess goodknowledge of Pap test and its purpose. These findings can be used in identifying prospect cervical cancer screeningsignificance populations and trend for future intrusion. 相似文献
77.
Raza SA Mahendran S Rahman N Williams RG 《The Journal of laryngology and otology》2002,116(12):1047-1049
Familial clustering of congenital bilateral abductor vocal fold paralysis has been reported very rarely. So far, only a handful of cases have been reported, mostly with the autosomal dominant of X-linked recessive mode of inheritance. We describe the cases of a brother and sister, who presented with neonatal stridor due to bilateral abductor vocal fold paralysis. First-degree parental consanguinity suggests an autosomal recessive mode of inheritance. Karyotype analysis revealed a paracentric balanced inversion of chromosome 13 in both cases, that was also present in the unaffected mother. An updated review of the literature on this interesting but rare condition is also presented. 相似文献
78.
79.
80.
BACKGROUND: Work experiences among early adolescents are largely undocumented. Our purpose was to document the prevalence of work and work-related injury among lower-income Hispanic South Texas middle school students. METHODS: Anonymous surveys were conducted in classrooms of sixth- through eighth-grade students, and 3,008 students reported current or recent employment. RESULTS: The prevalence of work was 56%; mean weekly work hours were 7.7. Increasing weekly work hours were significantly related to work injury (11-20 hours, odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1-1.9; 21+ hours, OR, 2.4; 95% CI, 1.8-3.2, compared with 1-10 hours). The odds of injury were highest for agriculture (OR, 4.4; 95% CI, 3.3-6.0), followed by restaurant (OR, 3.8; 95% CI, 2.7-5.4), construction (OR, 3.6; 95% CI, 2.4-5.2), and yard work (OR, 1.7; 95% CI, 1.4-2.2). CONCLUSION: Working more than 20 hours weekly increased the likelihood of injury among middle school students. Parents and professionals should monitor weekly school-year work hours. 相似文献