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991.
Marco Danova Monica Giordano Eugenio Erba Sergio Palmeri Vincenza Candiloro Alberto Riccardi Giovanni Ucci Giuliano Mazzini Maurizio D'Incalci Edoardo Ascari 《Journal of cancer research and clinical oncology》1992,118(8):575-580
Summary In many cell systems, resistance to cytotoxic drugs is acquired by the amplification and/or overexpression of the multidrug resistance (mdr) gene, which codes for the glycoprotein, p170 (P-glycoprotein). Moreover, in a variety of malignant tumours there is increasing evidence of the relationship between the DNA ploidy pattern of patients and their prognosis. In this study we aimed to evaluate these two potential indicators of constitutive drug resistance in human colorectal tumours. We employed a method to quantify simultaneously, on a per cell basis,mdr gene expression (using the C219 monoclonal antibody for P-glycoprotein) and nuclear DNA content with high-resolution bivariate flow cytometry. The study was performed on a human coloncarcinoma-derived cell line (LoVo) and its doxorubicinresistant variant (LoVo/Dx) and on tumour samples and adjacent normal mucosa from 35 untreated patients with colon cancer. The P-glycoprotein was found in both LoVo and LoVo/Dx cells with levels slightly lower in the parental than in the resistant subline (P, NS). A multidrug-resistant specific probe for mRNA expression and Western blot assay confirmed the specificity of p170 expression. All of the colon cancer with unimodal diploid DNA distribution and all the normal colonic mucosa samples showed P-glycoprotein expression, without a statistically significant difference in median values between tumours and normal samples. Tumours with bimodal DNA distribution showed median values of P-glycoprotein expression of their hyperdiploid cell clones significantly higher than those of their diploid clones and of the tumours with unimodal DNA distribution (P<0.005). Our results show the feasibility of bivariate flow-cytometric analysis of P-glycoprotein expression and DNA content on clinical material and support the hypothesis that the MDR phenotype and DNA ploidy together may influence the biological behaviour of colon cancer in vivo.Abbreviations MDR
multidrug resistance phenotype
-
mdr
multidrug resistance gene
- FITC
fluorescein isothiocyanate
- PBS
phosphate-buffered saline
Research supported in part by C.N.R. target projects Oncology and Biotechnology and Bioinstrumentation, by A.I.R.C. and by I.R.C.C.S. San Matteo 相似文献
992.
Cytochrome P450 2D6 genotype and steady state plasma levels of risperidone and 9-hydroxyrisperidone 总被引:9,自引:0,他引:9
The role of the polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of risperidone to its major active metabolite,
9-hydroxyrisperidone (9-OH-risperidone), has been documented after single oral doses of the drug. In this study, the influence
of the CYP2D6 polymorphism on the steady-state plasma concentrations of risperidone and 9-OH-risperidone was investigated.
Thirty-seven schizophrenic patients on monotherapy with risperidone, 4–8 mg/day, were genotyped by RFLP and PCR for the major
functional variants of the CYP2D6 gene. Steady state plasma levels of risperidone and 9-OH-risperidone were analysed by HPLC. Based on the genotype analysis,
three patients were classified as ultrarapid metabolizers (UM) with an extra functional CYP2D6 gene, 16 were homozygous extensive metabolizers (EM), 15 heterozygous EM and three poor metabolizers (PM). The median steady-state
plasma concentration-to-dose (C/D) ratios of risperidone were 0.6, 1.1, 9.7 and 17.4 nmol/l per mg in UM, homozygous EM, heterozygous
EM and PM, respectively, with statistically significant differences between PM and the other genotypes (P<0.02). The C/D of 9-OH-risperidone also varied widely but was not related to the genotype. The risperidone/9-OH-risperidone
ratio was strongly associated with the CYP2D6 genotype, with the highest ratios in PM (median 0.79). Heterozygous EM also had significantly higher ratios than homozygous
EM (median value 0.23 versus 0.04; P<0.01) or UM (median 0.03; P<0.02). No significant differences were found in the C/D of the sum of the plasma concentrations of risperidone and 9-OH-risperidone
between the genotype groups. In conclusion, the steady-state plasma concentrations of risperidone and the risperidone/9-OH-risperidone ratio are highly dependent on
the CYP2D6 genotype. However, as risperidone and 9-OH-risperidone are considered to have similar pharmacological activity, the lack
of relationship between the genotype and the sum of risperidone and 9-OH-risperidone indicates that the CYP2D6 polymorphism
may be of limited importance for the clinical outcome of the treatment.
Received: 3 March 1999 / Final version: 28 June 1999 相似文献
993.
Irene Franco Jean Piero Margaria Maria Chiara De Santis Andrea Ranghino Daniel Monteyne Marco Chiaravalli Monika Pema Carlo Cosimo Campa Edoardo Ratto Federico Gulluni David Perez-Morga Stefan Somlo Giorgio R. Merlo Alessandra Boletta Emilio Hirsch 《Journal of the American Society of Nephrology : JASN》2016,27(4):1135-1144
Signaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2α (PI3K-C2α) in renal tubule-derived inner medullary collecting duct 3 cells and show that PI3K-C2α resides at the recycling endosome compartment in proximity to the primary cilium base. In this subcellular location, PI3K-C2α controlled the activation of Rab8, a key mediator of cargo protein targeting to the primary cilium. Consistently, partial reduction of PI3K-C2α was sufficient to impair elongation of the cilium and the ciliary transport of polycystin-2, as well as to alter proliferation signals linked to polycystin activity. In agreement, heterozygous deletion of PI3K-C2α in mice induced cilium elongation defects in kidney tubules and predisposed animals to cyst development, either in genetic models of polycystin-1/2 reduction or in response to ischemia/reperfusion-induced renal damage. These results indicate that PI3K-C2α is required for the transport of ciliary components such as polycystin-2, and partial loss of this enzyme is sufficient to exacerbate the pathogenesis of cystic kidney disease. 相似文献
994.
Edoardo Botteri Giulio Tosti Massimo Barberis Laura Pala Angelo Battaglia Alessandra Clerici Giuseppe Spadola Emilia Cocorocchio Chiara Martinoli 《International journal of cancer. Journal international du cancer》2016,139(7):1618-1625
Cancer‐related inflammation may play an important role in disease progression and patient outcome, and could be easily monitored through indirect parameters routinely evaluated at diagnosis. Here, we investigated if peripheral blood cells and the ratios of neutrophils to lymphocytes (NLR) and of lymphocytes to monocytes (LMR) as surrogate markers of cancer related inflammation are associated with disease progression and survival of melanoma patients at any stage of the disease. Records of 1,182 melanoma patients included in an Institutional tumor registry in the period 2000–2010, were reviewed. Among them, 584 patients with a cutaneous or unknown primary melanoma and available pre‐operative blood tests were analyzed. Survival was estimated with the Kaplan–Meier method, and analyzed using Log‐rank test, Cox regression and multivariate Cox proportional hazard models. We found that patients presenting with distant metastases had higher leukocytes, neutrophils and monocytes, and lower lymphocytes compared to Stage I–III patients. Furthermore, at a single‐patient level, hematological profiles changed on disease progression from regional to distant metastatic, with significantly increased circulating leukocytes, neutrophils and monocytes, and decreased lymphocytes. Peripheral blood cell counts were not associated with survival of patients with a localized or regionally metastasized melanoma. Instead, in Stage IV patients, leukocytes (p = 0.001), neutrophils (p = 0.0002), monocytes (p = 0.002), NLR (p < 0.0001) and LMR (p = 0.005) were all significantly associated with survival, independently of other known prognostic factors. These results suggest that cellular components of peripheral blood do count for survival of patients with advanced melanoma. 相似文献
995.
Diabetes and periodontal disease: a case-control study 总被引:6,自引:0,他引:6
BACKGROUND: Periodontitis is often associated with diabetes and might be considered one of the chronic complications of diabetes mellitus, both in Type 1 (T1DM) and Type 2 (T2DM). This case-control study was designed to evaluate the possible association between non-insulin-dependent diabetes (T2DM) and clinical and microbiological periodontal disease among adult Sardinians. METHODS: A total of 212 individuals participated in this study: 71 T2DM patients aged 61.0 +/- 11.0 years and 141 non-diabetic controls in good general health aged 59.1 +/- 9.2 years. All subjects were given a clinical periodontal examination for probing depth, attachment level, presence of calculus, bleeding on probing, and assessment of plaque. Subgingival plaque samples were obtained, and P. gingivalis, P. intermedia, and T. forsythensis were identified using multiplex polymerase chain reaction. RESULTS: T2DM patients showed a significantly lower number of teeth present (P = 0.002); a significant increase in number of probing depths >4 mm, and percent of pocket depths >4 mm (P = 0.04 and P = 0.05, respectively); periodontitis (P = 0.046); bleeding on probing (P = 0.02); and plaque index (P = 0.01). A significant association with diabetes was detected for plaque (X2= 4.46; P <0.05) and bleeding on probing (X2= 3.60; P <0.05). Concerning bacteria prevalence, a positive association was detected for P. gingivalis (X2= 2.80; P <0.05) and T. forsythensis (X2= 3.87; P <0.05). Presence of plaque was positively associated with case status (odds ratio [OR] = 1.3; 95% confidence interval [CI]: 1.2, 3.6) and with prevalence of P. gingivalis and T. forsythensis (OR = 1.2, 95% CI: 1.3, 2.2; and 1.2, 95% CI: 1.2, 1.8, respectively). CONCLUSION: Patients with T2DM undoubtedly have a susceptibility for more severe periodontal disease. 相似文献
996.
Virgilio Edoardo Scorsi Alessandro Amodio Pietro Maria Goglia Angelo Macarone Palmieri Raffaele 《Clinical and experimental medicine》2016,16(3):479-480
Clinical and Experimental Medicine - 相似文献
997.
998.
Patanè F Patanè S Zingarelli E El Qarra S Trichiolo S 《International journal of cardiology》2008,125(2):e23-e24
Aortic regurgitation is associated with numerous eponymous signs. It has been reported severe aortic regurgitation also due to a quadricuspid aortic valve, a rare congenital anomaly. We present a case of revelation of quadricuspid aortic valve at left ventriculography with aortography in a 71-year-old Italian woman with severe aortic regurgitation. 相似文献
999.
1000.
Tikhonoff V Casiglia E Mazza A Scarpa R Thijs L Pessina AC Staessen JA 《Journal of the American Geriatrics Society》2005,53(12):2159-2164
OBJECTIVES: To investigate the role of low-density lipoprotein cholesterol (LDL-C) as a predictor of mortality in elderly subjects. DESIGN: Population-based prospective cohort study. SETTING: Two communities in northern Italy. PARTICIPANTS: Three thousand one hundred twenty Caucasian subjects aged 65 and older recruited in for the Cardiovascular Study in the Elderly and followed up for 12 years. MEASUREMENTS: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, glucose, creatinine, and body mass index. Clinical measures: medical assessment, diabetes mellitus, hypertension, stroke, coronary disease, heart failure, and smoking and drinking habits. Vital status measures: death certificates from the Registry Office and causes of death according to the International Classification of Diseases. After plotting mortality rates using quartiles of LDL-C, relative hazard rates (RHRs) were calculated using multivariate Cox regression analyses. When the trend was nonlinear, the RHRs were further calculated for the 25th, 50th, and 75th percentiles of the distribution to confirm curvilinearity. RESULTS: The distribution of risk of total mortality in women and of fatal heart failure in all subjects was curvilinear (non J-shaped), decreasing nonlinearly with LDL-C. For total mortality in men and cardiovascular mortality in both sexes, the relationship with LDL-C was J-shaped. The risk of fatal myocardial infarction was J-shaped in men, whereas it increased linearly with higher LDL-C in women. In both sexes, the association between stroke mortality and LDL-C was not significant. CONCLUSION: This study adds to the uncertainty of the role of elevated levels of LDL-C as a risk factor for mortality in old people. 相似文献