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51.
Kowalewski C Hamada T Wozniak K Kawano Y Szczecinska W Yasumoto S Schwartz RA Hashimoto T 《International journal of molecular medicine》2007,20(1):75-78
Epidermolysis bullosa simplex Weber-Cockayne type (EBS-WC) is a genetically inherited skin disease characterized by blistering restricted to the palms and soles. Its inheritance in nearly all kindreds is caused by a dominant-negative mutation in either KRT5 or KRT14, the genes encoding keratin 5 and keratin 14 proteins, respectively. Rarely, recessive mutations have also been found. We described a family with EBS-WC caused by a novel autosomal dominant mutation (G476D) in the keratin 5 gene. One family member was first seen with mucosal erosions and generalized blisters localized on the anogenital area, trunk, face and sites of mechanical trauma. Molecular analysis in this patient showed the presence of an additional mutation, an autosomal recessive (G183E) one, in the same gene. This observation suggests an additional effect of a recessively inherited mutation modulating the phenotypic expression of EBS caused by a partially dominant mutation and is important for accurate genetic counseling. 相似文献
52.
Monika Siołek Cezary Cybulski Danuta Gąsior‐Perczak Artur Kowalik Beata Kozak‐Klonowska Aldona Kowalska Małgorzata Chłopek Wojciech Kluźniak Dominika Wokołorczyk Iwona Pałyga Agnieszka Walczyk Katarzyna Lizis‐Kolus Ping Sun Jan Lubiński Steven A. Narod Stanisław Góźdż 《International journal of cancer. Journal international du cancer》2015,137(3):548-552
Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi‐organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer‐free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non‐carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age‐ and sex‐matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 + 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non‐carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid. 相似文献
53.
Grzegorz Sukiennicki Magdalena Muszyńska Katarzyna Jaworska-Bieniek Katarzyna Kaczmarek Wojciech Marciniak Marcin Lener Katarzyna Durda Tomasz Gromowski Tomasz Huzarski Tomasz Byrski Jacek Gronwald Oleg Oszurek Cezary Cybulski Tadeusz Dębniak Antoni Morawski Anna Jakubowska Jan Lubiński 《Hereditary cancer in clinical practice》2015,13(Z2):A5
54.
Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
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Joanne Kotsopoulos Jan Lubinski Jacek Gronwald Cezary Cybulski Rochelle Demsky Susan L. Neuhausen Charmaine Kim‐Sing Nadine Tung Susan Friedman Leigha Senter Jeffrey Weitzel Beth Karlan Pal Moller Ping Sun Steven A. Narod 《International journal of cancer. Journal international du cancer》2015,137(5):1136-1146
The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA‐associated ovarian cancer. Thus, we conducted a matched case–control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41–0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48–0.79) and 50% (95% CI 0.29–0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40–0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22–0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79–0.96; p‐trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81–1.19; p‐trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03–1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations. 相似文献
55.
Dominika Świerczyńska-Machura Jolanta Walusiak-Skorupa Ewa Nowakowska-Świrta Joanna Piasecka-Zelga Radosław Świercz Cezary Pałczyński 《International journal of occupational medicine and environmental health》2012,25(4):492-498
Objectives
Diisocyanates (DIC) are highly reactive, low-molecular-weight chemicals which are the leading cause of occupational asthma (OA). The aim of the study was to analyze certain aspects of the pathogenesis of allergic inflammation in the airways induced by toluene diisocyanate (TDI) in an experimental model in mice.Materials and Methods
The experiment was carried out on 50 female BALB/cJ/Han/IMP mice, which were exposed by inhalation (intranasal and in the inhalation chamber) to toluene diisocyanate (2,4-TDI). After the experiment, the bronchoalveolar lavage fluid (BALF) was collected from the animals, and the composition of the induced inflammatory cells, and the concentrations of certain cytokines (IL-4, IL-5, TNF-α) were evaluated.Results
The total number of cells in BALF of the examined group of mice was significantly higher compared to the control mice. There was also a significant increase in neutrophils and eosinophils in the study group compared to the controls. The number of lymphocytes and macrophages did not differ significantly between the two groups. A statistically significant increase in the level of TNF-α was shown to occur in the group exposed to toluene diisocyanate in comparison to the control group. The concentration of IL-4 increased in the study group, compared to the control one, but the differences did not reach the level of significance, p > 0.05. Such difference was not observed for IL-5.Conclusions
We developed a murine model of TDI-induced asthma which caused the influx of inflammatory cells like eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF) in the TDI-treated mice. The increase of the concentration of some proinflammatory cytokines (TNF-α, IL-4) in BALF from the exposed mice was also observed. 相似文献56.
Chmielak Z Ruzyllo W Demkow M Soroka M Karcz M Konka M Bekta P Kepka C 《The Journal of heart valve disease》2002,11(4):509-516
BACKGROUND AND AIMS OF THE STUDY: The outcome of percutaneous balloon mitral commissurotomy (BMC) has been reported as poor in patients with prior surgical commissurotomy. The study aim was to evaluate immediate and long-term follow up results of BMC in patients with restenosis after surgical commissurotomy compared to patients with 'de-novo' mitral stenosis. METHODS: Between October 1988 and September 1999, a total of 1,027 patients underwent BMC. Of these patients, 169 (16.5%) were examined at 17+/-7 years (range: 2-33 years) after surgical commissurotomy (group 1), and 858 (83.5%) had de-novo mitral stenosis (group 2). RESULTS: Group 1 patients were older than group 2 patients (49.4+/-9.3 versus 47.3+/-9.6 years; p <0.05), and atrial fibrillation was seen more often in group 1 (53.9% versus 32.4%; p <0.005). Before BMC, mitral valve area (MVA) was similar in both groups (1.18+/-0.27 and 1.15+/-0.26 cm2 in groups 1 and 2 respectively; p = NS); following BMC, MVA was 1.82+/-0.3 and 1.93+/-0.40 cm2 respectively (p <0.05). Four patients (2.4%) from group 1, and 24 (2.8%) from group 2 required mitral valve replacement due to severe regurgitation (p = NS). Annual clinical and echocardiographic evaluation was completed for 950 patients (mean follow up 56.2+/-31.1 months (range: 12-132 months). Cardiac events defined as death, valve surgery or repeat BMC occurred in 16.0% of patients in group 1, and in 9.6% of those in group 2. At follow up of three, five and 10 years, actuarial event-free survival was 85.7+/-2.9%, 79.8+/-3.8% and 65.2+/-7.5% respectively in group 1, and 93.4+/-0.9%, 90.1+/-1.1% and 72.7+/-3.9% respectively in group 2 (log rank test, p = 0.02). Multivariate analysis showed MVA <1.5 cm2 after BMC, mitral regurgitation grade >2/4, Wilkins score >8, and mean transmitral gradient and left atrial mean pressure post BMC to be independent predictors of an adverse event occurring during follow up. CONCLUSION: BMC in patients with restenosis after surgical commissurotomy is an effective method of treatment, and may help to avoid valve surgery in most patients. 相似文献
57.
Yi He Magdalena A. Mozolewska Pawe? Krupa Adam K. Sieradzan Tomasz K. Wirecki Adam Liwo Khatuna Kachlishvili Shalom Rackovsky Dawid Jagie?a Rafa? ?lusarz Cezary R. Czaplewski Stanis?aw O?dziej Harold A. Scheraga 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(37):14936-14941
58.
59.
Debniak T Scott RJ Huzarski T Byrski T Rozmiarek A Debniak B Załuga E Maleszka R Kładny J Górski B Cybulski C Gronwald J Kurzawski G Lubinski J 《Cancer research》2005,65(3):835-839
The population frequencies of the CDKN2A variants remain undetermined. In Poland there are three common variants of CDKN2A: an alanine to threonine substitution (A148T), Nt500c>g and Nt540c>t, which have been detected in other populations. To establish if they are associated with an increased malignant melanoma (MM) risk we did an association study based on genotyping 471 patients with MM and 1,210 random control subjects from the same Polish population. We found a significantly increased frequency of the A148T variant among patients with MM (7.0%) in comparison with the general population (2.9%). The incidence of the A148T variant remained greater in both unselected and familial melanoma subgroups. A statistically significant positive association was seen for unselected MM (odds ratio, 2.529; P = 0.0003), especially in patients diagnosed under 50 years of age (odds ratio, 3.4; P = 0.0002). The A148T carrier population (heterozygous G/A alleles) was more likely to have a relative with malignancy compared with the noncarrier population (57% versus 36%, respectively; P = 0.03). Further examination of the CDKN2A promoter sequence done in 20 melanoma patients with the A148T change (heterozygous G/A alleles) and 20 patients with MM without this alteration identified it was in linkage disequilibrium with a polymorphism in the promoter region at position P-493. We found no statistically significant overrepresentation of the Nt500c>g and the Nt540c>t polymorphisms in the Polish melanoma population. In conclusion, the A148T variant of the CDKN2A gene seems to be associated with an increased risk of development of MM. Additional studies are required to confirm whether this particular change is associated with increased risk of other nonmelanoma malignancies. 相似文献
60.
OBJECTIVE: We investigated whether basal cytokeratin (CK5/6 or CK17) expression had an impact on survival in patients with operable breast cancer. METHODS: Expression of CK5/6 or CK17 was analyzed by immunohistochemistry in 195 women with breast cancer. RESULTS: In total, 72 (37%) tumor samples were regarded as being positive for CK5/6 or CK17. The basal-like phenotype as defined by basal cytokeratin expression, lack of estrogen receptor (ER) and absence of HER2 overexpression was found in 48 (25%) cases. Positive staining for CK5/6 or CK17 was associated with worse prognosis when compared with patients negative for basal cytokeratins in all cases (5-year cancer-specific survival rate 59.4 vs. 77.5%, p = 0.0273) and in the node-negative group (70.5 vs. 90.8%, p = 0.0208) but not in the node-positive group (43.9 vs. 65.4%, p = 0.1182). To determine the real prognostic value of basal cytokeratins, survival in a group of ER-negative patients was analyzed depending on CK5/6 or CK 17 expression. No influence on survival was observed. The outcome of patients whose cancers were positive for cyclin E regardless of ER status was not changed by CK5/6 or CK17 expression. In multivariate analysis, independent prognostic factors affecting survival in the whole group included: nodal involvement, HER2 status and cyclin E expression. Neither ER status nor basal cytokeratin expression retained statistical significance. CONCLUSION: We demonstrated that the poor prognosis associated with the basal-like phenotype of breast cancer was determined by ER absence and cyclin E expression and not by CK5/6 or CK17 expression. 相似文献