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21.
Multicenter study of the molecular basis of thalassemia intermedia in different ethnic populations 总被引:2,自引:0,他引:2
Verma IC Kleanthous M Saxena R Fucharoen S Winichagoon P Raizuddin S Khan SN Akbari MT Izadyar M Kotea N Old JM Ioannou PA Khan B 《Hemoglobin》2007,31(4):439-452
We studied 325 thalassemia intermedia patients from Iran, India, Pakistan, Thailand, Mauritius and Cyprus to examine factors which influence the phenotype. The beta-thalassemia (thal) mutations were determined for 219 beta-thal/beta-thal and 106 beta-thal/Hb E [beta26(B8)Glu-->Lys, GAG-->AAG] thalassemia intermedia patients. Thirty-one different mutations were identified, and their combination gave rise to more than 44 different genotypes, of which 14 (31.8%) had the beta(0)/beta(0), 21 (47.7%) the beta(0)/beta(+) and nine (20.5%) the beta(+)/beta(+) types. Thus, the beta(+)-thal mutations were present in 68.2% of patients. alpha-Thalassemia mutations were present in frequencies higher than in the general population of all ethnic groups studied, as 45% of the patients carried alpha-thal mutations. Correlation of alpha-thal mutations with beta-globin mutations showed that the alpha-thal mutations were mainly co-inherited with the beta(+)-thal mutations. The XmnI (G)gamma polymorphic site at -158 (C-->T) was positive (T) in nine (8.8%) of 102 patients of the beta(+)/beta(+) genotype, and the percentage of both XmnI (G)gamma polymorphism [+/-] (T/C) and [+/+] (T/T) genotypes increased to 42.9 and 87.3, respectively, in the beta(0)/beta(+) and beta(0)/beta(0) patients. This polymorphism was found in the majority of beta(+)-thal/Hb E compound heterozygote patients (88.6%), and beta(0)-thal/Hb E patients (84.8%), suggesting that it could be linked to the Hb E chromosome. Therefore, the XmnI (G)gamma polymorphism at -158 (C-->T) was associated with beta(0)-thal mutations as well as the Hb E chromosome. The present study demonstrates that in cases of thalassemia intermedia with beta(+) mutations, the common ameliorating factor is the presence of alpha-thal mutations, while in cases with beta(0) mutations, the common ameliorating factor is the presence of the XmnI (G)gamma polymorphism at -158 (C-->T). 相似文献
22.
Thalassemia and abnormal hemoglobins are common genetic disorders in Asia. Thalassemia is not only an important public health problem but also a socio-economic problem of many countries in the region. The approach to deal with the thalassemic problem is to prevent and control birth of new cases. This requires an accurate identification of the couple at high risk for thalassemia. However, the diagnosis of thalassemia carrier states need several tests which are not practical for screening the population at large. Recently we have used two simple laboratory tests to screen for potential thalassemia carriers and hemoglobin E individuals. There is also a new development in using the automatic HPLC to diagnose thalassemic diseases and the carriers. This system gives both qualitative and quantitative analysis of hemoglobin components in the same run with good precision and reproducibility. The system has been applied to study thalassemia and abnormal Hb in adult and cord blood. This system has enabled us to do both prenatal and postnatal diagnosis of thalassemia within the few minutes. However, none of these screening tests can accurately give specific diagnosis of the thalassemia genotype. Specific thalassemia mutation can be carried out by DNA analysis. Many DNA techniques have been used for point mutation detection and small deletion. For the last few years there is a development of DNA chip technology that has been applied for thalassemia mutation as well. Clinically, thalassemia is very heterogeneous in the manifestation. In spite of seemingly identical genotypes, severity of beta thalassemic patients can vary greatly. Heterogeneity in the clinical manifestation of beta thalassemic diseases may occur from the nature of beta globin gene mutation, alpha thalassemia gene interaction and difference in the amount of Hb F production which is partly associated with a specific beta globin haplotype. However, there is still some beta thalassemia cases that have a mild clinical symptom without those known genetic fators interaction suggesting that there are other additional factors responsible for the mildness of the disease. 相似文献
23.
Nattawara Chaneiam Chatchawan Changtam Thongperm Mungkongdee Umaporn Suthatvoravut Pranee Winichagoon Jim Vadolas Apichart Suksamrarn Suthat Fucharoen Saovaros Svasti 《Annals of hematology》2013,92(3):379-386
Thalassemia is an inherited disorder of hemoglobin molecules that is characterized by an imbalance of α- and β-globin chain synthesis. Accumulation of unbound α-globin chains in erythroid cells is the major cause of pathology in β-thalassemia. Stimulation of γ-globin production can ameliorate disease severity as it combines with the α-globin to form fetal hemoglobin. We examined γ-globin-inducing effect of curcuminoids extracted from Curcuma longa L. and their metabolite reduced forms in erythroid leukemia K562 and human primary erythroid precursor cells. The results showed that curcuminoid compounds, especially bisdemethoxycurcumin are potential γ-globin enhancers. We also demonstrated that its reduced analog, hexahydrobisdemethoxycurcumin (HHBDMC), is most effective and leads to induction of γ-globin mRNA and HbF in primary erythroid precursor cells for 3.6?±?0.4- and 2.0?±?0.4-folds, respectively. This suggested that HHBDMC is the potential agent to be developed as a new therapeutic drug for β-thalassemia and related β-hemoglobinopathies. 相似文献
24.
Taher AT Porter J Viprakasit V Kattamis A Chuncharunee S Sutcharitchan P Siritanaratkul N Galanello R Karakas Z Lawniczek T Ros J Zhang Y Habr D Cappellini MD 《Blood》2012,120(5):970-977
Nontransfusion-dependent thalassemia (NTDT) patients may develop iron overload and its associated complications despite receiving only occasional or no transfusions. The present 1-year, randomized, double-blind, placebo-controlled THALASSA (Assessment of Exjade in Nontransfusion-Dependent Thalassemia) trial assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients. A total of 166 patients were randomized in a 2:1:2:1 ratio to starting doses of 5 or 10 mg/kg/d of deferasirox or placebo. The means ± SD of the actual deferasirox doses received over the duration of the study in the 5 and 10 mg/kg/d starting dose cohorts were 5.7 ± 1.4 and 11.5 ± 2.9 mg/kg/d, respectively. At 1 year, the liver iron concentration (LIC) decreased significantly compared with placebo (least-squares mean [LSM] ± SEM, -2.33 ± 0.7 mg Fe/g dry weight [dw], P = .001, and -4.18 ± 0.69 mg Fe/g dw, P < .001) for the 5 and 10 mg/kg/d deferasirox groups, respectively (baseline values [means ± SD], 13.11 ± 7.29 and 14.56 ± 7.92 mg Fe/g dw, respectively). Similarly, serum ferritin decreased significantly compared with placebo by LSM -235 and -337 ng/mL for the deferasirox 5 and 10 mg/kg/d groups, respectively (P < .001). In the placebo patients, LIC and serum ferritin increased from baseline by 0.38 mg Fe/g dw and 115 ng/mL (LSM), respectively. The most common drug-related adverse events were nausea (n = 11; 6.6%), rash (n = 8; 4.8%), and diarrhea (n = 6; 3.6%). This is the first randomized study showing that iron chelation with deferasirox significantly reduces iron overload in NTDT patients with a frequency of overall adverse events similar to placebo. 相似文献
25.
ABSTRACT: Background: Few studies of immigrant women's views of maternity care in their new homelands have been conducted. In Victoria, Australia, approximately 1 woman in 7 giving birth was born overseas in a non‐English speaking country. This paper examines the views of three groups of immigrant women about the care they received in hospital for the birth of their babies and compares the findings with a population‐based statewide survey. Methods: Mothers in a New Country was a study of 318 Vietnamese, Turkish, and Filipino women interviewed about their maternity care experiences by bicultural interviewers 6 months after giving birth in Melbourne, Australia. The interview schedule was adapted from the 1994 Victorian Survey of Recent Mothers, a population‐based postal survey of 1336 women. Results: Of the 3 groups, 27 percent of Vietnamese, 48 percent of Turkish, and 39 percent of Filipino women reported their care during labor and birth as “very good,” figures significantly lower than for the statewide survey, in which 61 percent of women experiencing similar models of care described their care as “very good.” This significant differential in views about care was also present for many individual aspects of care. In the current study of mothers in a new country, comments about aspects of care with which women were particularly happy and unhappy highlighted their appreciation of care that was safe, kind, supportive, and respectful, and conversely, illustrated how distressed women were when care failed to meet these basic standards. Conclusions: What immigrant women wanted from their maternity care proved to be extremely similar to what Australian‐born women—and women the world over—want. Unfortunately, immigrant women were much less likely to experience care that gave them what they wanted. (BIRTH 29:4 December 2002) 相似文献
26.
Somboonthum P Yoshii H Okamoto S Koike M Gomi Y Uchiyama Y Takahashi M Yamanishi K Mori Y 《Vaccine》2007,25(52):8741-8755
We constructed a recombinant varicella-zoster virus (VZV) Oka vaccine strain (vOka) that contained the mumps virus (MuV) hemagglutinin-neuraminidase (HN) gene, inserted into the site of the ORF 13 gene by using the bacterial artificial chromosome (BAC) system in Escherichia coli. Insertion of the HN gene into the VZV genome was confirmed by PCR and Southern blot. The infectious virus reconstituted from the vOka-HN genome (rvOka-HN) had a growth curve similar to the original recombinant vOka without the HN gene. The mumps virus HN protein expressed in rvOka-HN infected cells was expressed diffusely in the cytoplasm, and modification of the protein was similar to that seen in MuV-infected cells. Electron microscopic examination of infected cells revealed that HN was expressed on the plasma membrane of the cells but not in the viral envelope, suggesting that the tropism of rvOka-HN would be unchanged from that of the original vOka strain. Immunization of guinea pigs with rvOka-HN-induced VZV- and HN-specific antibodies. Interestingly, the induced antibodies had a strong neutralizing activity against virus-cell infections of both MuV and VZV. Therefore, the novel varicella vaccine expressing MuV HN protein is suitable as a polyvalent live attenuated vaccine against VZV and MuV infections. 相似文献
27.
Journal of Cross-Cultural Gerontology - Exercise programmes are effective in reducing falls but few older people consider doing an exercise programme for falls prevention. This paper examines older... 相似文献
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Tankanitlert J Howard TA Temsakulphong A Sirankapracha P Morales NP Sanvarinda Y Fucharoen P Ware RE Fucharoen S Chantharaksri U 《European journal of clinical pharmacology》2006,62(9):743-748