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11.
Herbert Pichler Anja Möricke Georg Mann Andrea Teigler‐Schlegel Felix Niggli Karin Nebral Margit König Andrea Inthal Daniela Krehan Michael N. Dworzak Dasa Janousek Jochen Harbott Martin Schrappe Helmut Gadner Sabine Strehl Oskar A. Haas Renate Panzer‐Grümayer Andishe Attarbaschi 《British journal of haematology》2010,149(1):93-100
The presence of a dicentric chromosome dic(9;20) has been reported to have an unfavourable prognosis in children with B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL). As outcome may be influenced by type and composition of treatment, we analyzed 19 BCP‐ALL patients with dic(9;20) who have been treated with ALL‐BFM (Berlin‐Frankfurt‐Münster) protocols that included a 4‐drug induction and subsequent consolidation therapy. All patients were good responders to prednisone and in complete remission after induction therapy. Eight patients had no molecular disease after induction and another eight patients had levels ≤10?4 after consolidation therapy. After a median follow‐up of 3·4 years, probabilities of 5‐year event‐free and overall survival were 75 ± 11% and 94 ± 6%, respectively. Of note, there was a tendency for extramedullary disease in case of relapse (two of three relapses with central nervous system involvement). In conclusion, in the context of ALL‐BFM protocols dic(9;20)‐positivity appeared to have a favourable prognosis, which could be due to a dose‐ and time‐intensified induction and induction consolidation therapy. Given that in vitro studies have shown high cellular sensitivity of dic(9;20)‐positive leukemic blasts to l ‐asparaginase and cytarabine, it is reasonable to speculate that both drugs, as given early during BFM‐like induction and consolidation therapy, may have contributed to this good outcome. 相似文献
12.
Petr Lemež Andishe Attarbaschi Marie C. Béné Yves Bertrand Gianluigi Castoldi Erik Forestier Richard Garand Oskar A. Haas Sandrine Kagialis‐Girard Wolf‐Dieter Ludwig Estella Matutes Ester Mejstříková Marie‐Pierre Pages Winfried Pickl Anna Porwit Alberto Orfao Richard Schabath Jan Starý Herbert Strobl Pascaline Talmant Mars B. Van′t Veer Zuzana Zemanová 《European journal of haematology》2010,85(4):300-308
Objectives: Patients with near‐tetraploid (karyotype: 81 – 103 chromosomes) acute lymphoblastic leukemia (NT‐ALL) constitute about 1% of childhood ALL and data reported on them are limited and controversial. The aim of the study was to enlarge the knowledge on these rarely occurring ALL. Methods: The members of the European Group for Immunophenotyping of Leukemias (EGIL) searched retrospectively their databases for NT‐ALL patients. Results: We collected data of 36 European children from seven European countries with NT‐ALL diagnosed since 1992. All patients reached complete remission (CR) after induction chemotherapy. Their blasts were negative for peroxidase and BCR‐ABL1. Ten children were diagnosed as T‐cell ALL (T‐ALL) EGIL categories (T‐I n = 2, T‐II n = 2, T‐III n = 3, T‐IV n = 3) and four displayed various structural chromosomal abnormalities. Eight of 10 T‐ALL remained in 1st CR; one died in CR from sepsis and one is alive in 2nd CR. Median survival was 88 (7–213) months. B‐cell precursor (BCP) ALL was diagnosed in 26 children. Thirteen were positive for ETV6‐RUNX1 and are alive in 1st CR for 32–147 months. Ten children were ETV6‐RUNX1 negative and remained in 1st CR for 16–163 months. One girl with hypodiploid and NT metaphases and ETV6‐RUNX1‐negative BCP‐ALL and one of two boys with NT‐BCP‐ALL not examined for ETV6‐RUNX1 died of infection after stem cell transplantation in 2nd/3rd CR. Secondary myelodysplastic syndrome developed in two patients with NT‐BCP‐ALL. Conclusions: Our data demonstrate immunophenotypic, cytogenetic, and molecular heterogeneity of NT‐ALL and favorable prognosis of most NT‐ALL across different immunophenotypic and/or genetic ALL subtypes. 相似文献
13.
14.
Etzler J Peyrl A Zatkova A Schildhaus HU Ficek A Merkelbach-Bruse S Kratz CP Attarbaschi A Hainfellner JA Yao S Messiaen L Slavc I Wimmer K 《Human mutation》2008,29(2):299-305
Heterozygous germline mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 cause hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, a dominantly inherited cancer susceptibility syndrome. Recent reports provide evidence for a novel recessively inherited cancer syndrome with constitutive MMR deficiency due to biallelic germline mutations in one of the MMR genes. MMR-deficiency (MMR-D) syndrome is characterized by childhood brain tumors, hematological and/or gastrointestinal malignancies, and signs of neurofibromatosis type 1 (NF1). We established an RNA-based mutation detection assay for the four MMR genes, since 1) a number of splicing defects may escape detection by the analysis of genomic DNA, and 2) DNA-based mutation detection in the PMS2 gene is severely hampered by the presence of multiple highly similar pseudogenes, including PMS2CL. Using this assay, which is based on direct cDNA sequencing of RT-PCR products, we investigated two families with children suspected to suffer from MMR-D syndrome. We identified a homozygous complex MSH6 splicing alteration in the index patients of the first family and a novel homozygous PMS2 mutation (c.182delA) in the index patient of the second family. Furthermore, we demonstrate, by the analysis of a PMS2/PMS2CL "hybrid" allele carrier, that RNA-based PMS2 testing effectively avoids the caveats of genomic DNA amplification approaches; i.e., pseudogene coamplification as well as allelic dropout, and will, thus, allow more sensitive mutation analysis in MMR deficiency and in HNPCC patients with PMS2 defects. 相似文献
15.
16.
Steiner M Hochreiter D Kasper DC Kornmüller R Pichler H Haas OA Pötschger U Hutter C Dworzak MN Mann G Attarbaschi A 《Leukemia & lymphoma》2012,53(9):1682-1687
A recent study suggested that mesenchymal cells in bone marrow (BM) may counteract l-asparaginase (L-Asp)-containing acute lymphoblastic leukemia (ALL) therapy by secreting asparagine. Herein, we compared asparagine and aspartic acid concentrations in the BM and peripheral blood (PB), in order to determine whether this in vitro observation could be translated into in vivo differences of amino acid levels between both compartments. Asparagine and aspartic acid concentrations in BM (days 15 and 33) and PB (days 12, 15 and 33) were measured during L-Asp-containing Berlin-Frankfurt-Münster (BFM)-based 5-week multi-agent remission induction therapy in 11 children diagnosed with ALL at the St. Anna Children's Hospital in Vienna, Austria. The level of asparagine depletion did not differ significantly between both compartments at any time point measured, but aspartic acid concentrations were significantly higher in BM than PB at days 15 and 33 (p < 0.05). In the context of the reported mesenchymal asparagine production in BM, an increased asparagine production may indeed take place in BM. However, it may be overcome by continuous action of L-Asp, which is mirrored by increased aspartic acid levels but unchanged low asparagine levels in BM, suggesting a higher BM turnover of asparagine generated by L-Asp during induction therapy. 相似文献
17.
Mohammad Hasan Lotfi Hossein Fallahzadeh Masoud Rahmanian Hossein Lashkardoost Andishe Hamedi 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2018,12(5):705-709
Background
Gestational diabetes mellitus (GDM) has occurred in Fourteen percent of all pregnancies in the world. Epidemiological evidences about risk factors of GDM may be different from region to region and are unknown, exactly. This study examines the role of clinical factors in the association of gestational diabetes in Yazd, Iran.Methods
This study was carried out on 168 women with gestational diabetes and 168 women as controls after matching for age and place of residence. Each participant was interviewed about her pregnancy history and tobacco consumption. Information including BMI, weight before pregnancy and background of underlying diseases were recorded from information system in Health Centers. Finally, data were analyzed by using chi-square test, logistic regression and multiple correspondence analyze(MCA).Results
History of gestational diabetes in past pregnancy OR?=?3.2[95%CI:1.1, 9.7], a family history of gestational diabetes OR?=?3.7 [95%CI:1.1, 11.5], a history of hookah smoking OR?=?3.6 [95%CI:1.06, 12.3], being obese before pregnancy OR?=?1.9[95%CI:1.01, 3.5], and weight gain during pregnancy OR?=?0.5[95%CI:0.2, 0.9], were the most important determinants of gestational diabetes. There were not significant relation between GDM and underlying diseases, history of stillbirth, abortion, twinning, cigarette smoking, alcohol and drug abuse.Conclusions
In this research modifiable risk factors for gestational diabetes were high BMI before pregnancy, weight gain during pregnancy and history of hookah consumption. We advise that appropriate education, avoiding sedentary lifestyle, diet improvement and advertising which focus on tobacco consumption is playing as an important role in developing the chronic diseases, including GDM. 相似文献18.
19.
Seyed-Javad Pournaghi Farhad Barazandeh Noveyri Hadi Mohammad Doust Ali Ahmadi Andishe Hamedi Jamileh Rahimi 《Nutrition and cancer》2013,65(7):1094-1099
Aim: Esophageal cancer (EC) is considered one of the most common types of cancer in the world. High intake of dietary proteins is suggested to increase EC. This study examined associations between intake of red meats, processed meat, poultry, and fish and the risk of EC.Methods: This hospital-based Case–Control study included 96 people with EC and 187 people without EC from Bojnurd, Iran. Socio-demographic data was collected from all participants at enrollment using general information questionnaire. Dietary intake was assessed using a validated 168 item semi-quantitative food frequency questionnaire.Results: After adjusting for potential confounders, there was a significant association between the consumption of beef (P?=?0.04), processed meats (sausages) (P?=?0.01), and chicken with skin (P?=?0.001) with the risk of EC.Conclusion: We observed a positive association between red meat, processed meats (sausages), chicken with skin and the risk of EC. The use of lamb meat and fish had no significant association with the risk of EC. 相似文献
20.
Steiner M Matthes-Martin S Attarbaschi A Minkov M Grois N Unger E Holter W Vormoor J Wawer A Ouachee M Woessmann W Gadner H 《Bone marrow transplantation》2005,36(3):215-225
Children with multisystem Langerhans cell histiocytosis (LCH) and risk organ involvement who fail to respond to conventional chemotherapy have an extremely poor prognosis. Myeloablative stem cell transplantation (SCT) as a possible salvage approach for these patients has been associated with a high risk of transplant-related mortality. Therefore, allogeneic stem cell transplantation following a reduced-intensity conditioning regimen (RIC-SCT) has recently been performed as an alternative salvage approach. We report on the experience with allogeneic RIC-SCT in nine pediatric high-risk LCH patients. Conditioning regimen included fludarabine in all patients, melphalan in eight patients, total lymphoid irradiation in six patients, total body irradiation in two, antithymocyte globulin in five, and Campath in four patients. RIC-SCT was well tolerated with regard to common procedure-related complications. Two patients died 50 and 69 days after RIC-SCT, respectively. Seven out of the nine patients survived and showed no signs of disease activity (including one with nonengraftment and full autologous hematopoietic recovery) after median follow-up of 390 days post-SCT. Based on this observation, we conclude that RIC-SCT is a feasible procedure with low transplant-related morbidity and mortality and a promising new salvage approach for high-risk LCH patients with resistant risk organ involvement. 相似文献