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1.

Objectives

The aim of the study was to characterize the differences in the frequencies of NS3 and NS5A resistance-associated variants (RAVs) among Polish therapy-naive genotype 1 (G1) hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients including clustering patterns and association of RAV frequency with liver fibrosis.

Methods

NS3/NS5A RAVs were identified by population sequencing in 387 directly acting antiviral treatment-naive G1-infected individuals (54 with genotype 1a (G1a) and 333 with genotype 1b (G1b)). Liver fibrosis was assessed based on histopathology or ultrasound elastography. Phylogenetic clusters were identified using maximum likelihood models. For statistics, chi-squared or two-sided Fisher's exact tests and multivariate logistic regression models were used, as appropriate.

Results

NS3 RAVs were found in 33.33% (18/54) for G1a and 2.62% (8/297) for G1b whereas NS5A variants were present in 5.55% (3/54) G1a and 9.31% (31/333) G1b sequences. Variations in NS5A 31 and 93 codon positions were found only in G1b (4.2% (14/333) for L31I/F/M and 5.39% (17/333) for Y93H). NS5A RAVs were more frequent among patients with advanced liver fibrosis (17.17% (17/99) for F3–F4 versus 6.94% (17/245) for F0–F2; p 0.004) or liver cirrhosis (20.34% (12/59) for F4 versus 7.72% (22/285) for F0–F3; p 0.003). Liver cirrhosis (F4) was associated with higher odds ratio of the NS5A RAVs among HCV-infected patients (odds ratio 2.34, 95% CI 1.004–5.291; p 0.049). NS5A RAVs were less frequent among sequences forming clusters and pairs (5.16% (8/155) versus 11.21% (26/232); p 0.039).

Conclusions

Presence of NS5A RAVs correlated with progression of liver fibrosis and represents de novo selection of variants rather than transmission of drug resistance. Hence, the presence of NS5A RAVs may be a predictor for a long-lasting HCV infection.  相似文献   
2.
In this report, we present two cases of axillary lymph node metastatic breast carcinoma with features mimicking ductal carcinoma in situ (DCIS): one was of the comedo-like type and the other was suggestive of the micropapillary type. In the first case, the primary tumor presented DCIS of the comedo type; however, in the second case, the primary tumor consisted only of the invasive ductal component. Immunohistochemistry against smooth muscle actin, S100-protein, CK5/6, CD10, P63, and 34betaE12 did not identify myoepithelial cells either in DICS of the first primary tumor or in both metastases. These features probably do not represent the true DCISs, but only mimic them. This observation suggests that a proportion of "primary DCIS" may constitute an invasive pseudo-DCIS carcinoma, and immunohistochemical identification of myoepithelial cells may be helpful in such cases.  相似文献   
3.
In our study we have examined allelic variation of codon 129 among the Polish population as well as Polish and Dutch CJD cases. The open reading frame of the PrP gene was amplified using the polymerase chain reaction (PCR). PCR product was digested with Nsp I and Mae II endonucleases and separated by 2% agarose gel electrophoresis and, finally, sequenced by the Sanger dideoxy-mediated chain-termination method. To obtain population data we have screened 109 unrelated Polish adults. There were 45% of methionine homozygotes, 16% of valine homozygotes and 3% of heterozygotes. Among Polish CJD cases, 75% were methionine homozygous, 12.5% were valine homozygous and 12.5% were heterozygous, whereas among Dutch CJD cases it was 29% of Met/Met and 71% of Met/Val genotypes.  相似文献   
4.
Immunohistochemistry is widely used for diagnostic neuropathology, but contrary to some anxieties--it is not method which may replace an experienced pathologist. On the contrary--only an experienced pathologist may use this method safely. If the differential diagnosis is wrong, the results may be misleading. Similarly, the specificity of used antibodies does not guarantee the clearcut differentiation.  相似文献   
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Analysis of gene expression data suggests that breast cancers are divisible into molecular subtypes which have distinct clinical features. This study evaluates whether pathologic features and etiologic associations differ among molecular subtypes. We evaluated 804 women with invasive breast cancers and 2,502 controls participating in a Polish Breast Cancer Study. Immunohistochemical stains for estrogen receptor alpha, progesterone receptor, human epidermal growth factor receptors (HER2 and HER1), and cytokeratin 5 were used to classify cases into five molecular subtypes: luminal A, luminal B, HER2-expresing, basal-like, and unclassified. Relative risks were estimated using adjusted odds ratios and 95% confidence intervals. We observed that compared with the predominant luminal A tumors (69%), other subtypes were associated with unfavorable clinical features at diagnosis, especially HER2-expressing (8%) and basal-like (12%) tumors. Increasing body mass index significantly reduced the risk of luminal A tumors among premenopausal women (odds ratios, 0.71; 95% confidence intervals, 0.57-0.88 per five-unit increase), whereas it did not reduce risk for basal-like tumors (1.18; 0.86-1.64; P(heterogeneity) = 0.003). On the other hand, reduced risk associated with increasing age at menarche was stronger for basal-like (0.78; 0.68-0.89 per 2-year increase) than luminal A tumors (0.90; 0.95-1.08; P(heterogeneity) = 0.0009). Although family history increased risk for all subtypes (except for unclassified tumors), the magnitude of the relative risk was highest for basal-like tumors. Results from this study have shown that breast cancer risk factors may vary by molecular subtypes identified in expression studies, suggesting etiologic, in addition to clinical, heterogeneity of breast cancer.  相似文献   
8.
We present an unusual case of diffuse large B-cell lymphoma within pontocerebellar angle schwannoma in 62-year-old woman. The patient suffered for 5 months with V, VII and VIII nerves paresis and with cerebellar ataxia. CT scan demonstrated large hyperdensive mass in cerebellopontine angle translocating cerebellar hemisphere and cerebral trunk. The patient was subjected to surgery and the tumour was removed totally by suboccipital retromastoidal right craniectomy approach. Histopathological examination revealed schwannoma infiltrated with high grade B-cell lymphoma. The patient did well following surgery without any other lymphoma manifestations, and she died from a heart attack 20 months later. Solitary lymphoma of pontocerebellar angle coexisting with schwannoma is an unusual finding, thus our case is the first report.  相似文献   
9.
Intrauterine and intrapartum infections in newborn infants are still difficult to recognise. The newborn does not manifest the classic clinical signs of infection usually observed in children and adults and up to now there is no good laboratory marker. In the last few years, procalcitonin (PCT) has been found to increase during different inflammatory processes, especially bacterial ones. In this study we analysed the clinical value of PTC in parturient, umbilical cord and newborn blood for predicting perinatal infection. MATERIAL AND METHODS: Thirty parturients with symptoms of intrauterine infection were classified for this study. Blood samples were obtained from the mother, the umbilical cord and the newborn on the second day of life. Serum was stored at -70 degrees C and thawed at the time of analysis. Among the newborns there were 21 infants without and 9 with symptoms and signs of infection. PCT concentration was measured by immunoluminometric assay--LUMI test PCT (BRAHMS). RESULTS: Statistically significant results were found on the second day of life: 5.83 (4.70) ng/ml in ill, 1.41 (0.68) ng/ml in healthy (p < 0.0005). We observed a significant correlation between PCT concentration in mother and umbilical cord blood (y = 0.40x + 1.06; p < 0.05), as well as between umbilical cord blood and venous blood on the second day of life in newborns (y = 0.16x 1.21; p < 0.01). CONCLUSIONS: Measurement of PCT concentration in perinatal period in the mother and in umbilical cord blood of the newborn may be useful for early diagnosis and monitoring of infectious complications in neonates. We need more data on reference ranges of PCT concentration in pregnant women, parturients and umbilical cord blood.  相似文献   
10.
Coexistence of B-cell chronic lymphocytic leukemia (B-CLL) and chronic myelomonocytic leukemia (CMML) is an unusal event, and to our knowledge, only four such cases have been reported in the literature. We report a 68-year-old white woman in whom these two diseases were diagnosed concomitantly. The diagnosis was made on the basis of peripheral blood count, morphology and immunophenotyping, and bone marrow cytology and histology. Interphase FISH analysis detected a 13q14.3 deletion in lymphocytes nuclei and no such abnormality in monocytes nuclei. The PCR analysis of IgH gene rearrangement in the bone marrow, as well as the peripheral blood lymphocytes, showed two different monoclonal IgH configurations as the result of biallelic clonal rearrangement of IgH genes suggesting an origin of lymphocytes from B-cell progenitors. The patient was originally treated with prednisone 1 mg/kg/day because of progressive significant thrombocytopenia, without improvement. Subsequently, she received one course of cladribine (2-CdA). Significant reduction of lymphocytes in the peripheral blood was observed. However, rapid increase of monocytes was seen shortly after the 2-CdA treatment. Subsequently, she received hydroxyurea (1.5 g/day) without hematological improvement. The patient died in January 2003, three months after diagnosis because of progression of both leukemias and associated pneumonia. Possible etiopathogenic relationship between both disorders is discussed.  相似文献   
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