全文获取类型
收费全文 | 614篇 |
免费 | 26篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 28篇 |
妇产科学 | 14篇 |
基础医学 | 156篇 |
口腔科学 | 1篇 |
临床医学 | 36篇 |
内科学 | 68篇 |
皮肤病学 | 2篇 |
神经病学 | 45篇 |
特种医学 | 36篇 |
外科学 | 51篇 |
综合类 | 1篇 |
预防医学 | 20篇 |
眼科学 | 32篇 |
药学 | 33篇 |
肿瘤学 | 110篇 |
出版年
2022年 | 7篇 |
2021年 | 11篇 |
2019年 | 7篇 |
2018年 | 17篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 10篇 |
2014年 | 16篇 |
2013年 | 24篇 |
2012年 | 42篇 |
2011年 | 31篇 |
2010年 | 33篇 |
2009年 | 17篇 |
2008年 | 42篇 |
2007年 | 40篇 |
2006年 | 40篇 |
2005年 | 41篇 |
2004年 | 35篇 |
2003年 | 30篇 |
2002年 | 27篇 |
2001年 | 9篇 |
2000年 | 7篇 |
1999年 | 11篇 |
1998年 | 9篇 |
1997年 | 16篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 10篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 2篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1967年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有641条查询结果,搜索用时 15 毫秒
101.
Tone Ikdahl Andersen Hans Geir Eiken Fergus Couch Grete Kaada Martina Skrede Hilde Johnsen Thomas A. Aloysius Kjell M. Tveit Lisbeth Tranebjrg Anne Drum Pl Mller Barbara L. Weber Anne-Lise Brresen-Dale 《Human mutation》1998,11(2):166-174
Screening for mutations in the breast and ovarian cancer susceptibility gene, BRCA1, is complicated by the wide spectrum of mutations found in this large gene. In the present study a constant denaturant gel electrophoresis (CDGE) mutation screening strategy was established for ˜80% of the genomic coding sequence (exons 2, 11, 13–16, 20, 24). This strategy was applied to screen genomic DNA from 50 familial breast and/or ovarian cancer patients who had previously been examined for BRCA1 mutations by SSCP. A total of 14 carriers of 12 distinct disease-associated mutations and 7 carriers of 6 distinct rare substitutions leading to amino acid substitutions were identified. The SSCP failed to detect 40% of the different deletions/insertions (4/10) and 75% (6/8) of the different base substitutions leading to terminating codons or rare amino acid changes. SSCP did, however, identify one rare base substitution that could not be detected in the CDGE screening. To evaluate the CDGE mutation screening strategy further, 25 unrelated patients from Norwegian breast and/or ovarian cancer families were examined for BRCA1 mutations using a combined genomic DNA/cDNA approach covering the entire coding sequence of the gene. A total of six mutation carriers were detected, all of whom had cases of ovarian cancer in their families. Three patients from independent families carried an 1135insA mutation in exon 11, two others had a Gly484ter and an 1675delA mutation, respectively, and the sixth carried a splice mutation (5194-2 a→c) causing deletion of exon 18. CDGE may become an efficient tool in diagnostic and population based screening for BRCA1 mutations. Hum Mutat 11:166–174, 1998. © 1998 Wiley-Liss, Inc. 相似文献
102.
Hanne Skomedal Gunnar B. Kristensen Vera M. Abeler Anne-Lise Brresen-dale Claes Trop Ruth Holm 《The Journal of pathology》1997,181(2):158-165
Three hundred and seventy-four early-stage ovarian tumours, including 27 borderline tumours and 347 stage I carcinomas, were investigated immunohistochemically for overexpression of the TP53 and MDM2 proteins. TP53 (p53) and MDM2 alterations were detected in 15 and 4 per cent of borderline tumours, and in 50 and 13 per cent of stage I carcinomas, respectively. Mutations in the TP53 gene (exons 5–8) were demonstrated in 29 of the 50 stage I carcinomas studied, using denaturing gel electrophoresis followed by direct sequencing. TP53 overexpression was seen less often in tumours of mucinous and endometrioid type than in tumours of other histological types and more often in moderately and poorly differentiated than in well differentiated tumours. MDM2 protein overexpression was seen more often in clear cell carcinoma than in tumours of other histological types. These results indicate that TP53 abnormalities play a crucial role, and MDM2 abnormalities a minor role, in the development of early-stage ovarian carcinoma. There was no significant association between TP53 or MDM2 alterations and survival in multivariate analysis. © 1997 John Wiley & Sons, Ltd. 相似文献
103.
104.
Gerard-Blanluet M Port-Lis M Baumann C Perrin-Sabourin L Ebrad P Audry G Delezoide AL Verloes A 《American journal of medical genetics. Part A》2010,(11):2870-2874
Prune-belly sequence (PBS) usually results from early urethral obstruction. In rare cases, PBS seems to be due to a faulty primary development of the parietal mesenchyme leading to underdevelopment of the abdominal wall musculature, and disorganization of the smooth muscles in the urinary tract. We report on two patients with segmental, unilateral wall musculature deficiency associated with homolateral agenesis of ribs. One patient also had hemivertebrae and the other one ipsilateral diaphragmatic eventration and aplasia cutis. This combination of anomalies may represent a localized deficiency in the development of somitic mesoderm mesenchyme during early embryogenesis. 相似文献
105.
Olivier Capitain Andreaa Asevoaia Michele Boisdron-Celle Anne-Lise Poirier Alain Morel Erick Gamelin 《Clinical colorectal cancer》2012,11(4):263-267
BackgroundTo compare the efficacy and safety of pharmacokinetically (PK) guided fluorouracil (5-FU) dose adjustment vs. standard body-surface-area (BSA) dosing in a FOLFOX (folinic acid, fluorouracil, oxaliplatin) regimen in metastatic colorectal cancer (mCRC).Patients And MethodsA total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy. The comparison arm consisted of 39 patients, and these patients were also treated with FOLFOX with 5-FU by BSA. For the PK-adjusted arm 5-FU was monitored during infusion, and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range (5-FUODPM Protocol).ResultsThe objective response rate was 69.7% in the PK-adjusted arm, and median overall survival and median progression-free survival were 28 and 16 months, respectively. In the traditional patients who received BSA dosage, objective response rate was 46%, and overall survival and progression-free survival were 22 and 10 months, respectively. Grade 3/4 toxicity was 1.7% for diarrhea, 0.8% for mucositis, and 18% for neutropenia in the dose-monitored group; they were 12%, 15%, and 25%, respectively, in the BSA group.ConclusionsEfficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing. Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC. 相似文献
106.
107.
108.
Vilde D Haakensen Margarethe Biong Ole Christian Lingj?rde Marit Muri Holmen Jan Ole Frantzen Ying Chen Dina Navjord Linda Romundstad Torben Lüders Ida K Bukholm Hiroko K Solvang Vessela N Kristensen Giske Ursin Anne-Lise B?rresen-Dale ?slaug Helland 《Breast cancer research : BCR》2010,12(4):R65
Introduction
Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known.Methods
Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD.Results
SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5''-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified.Conclusions
Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer. 相似文献109.
110.
Lecoq A Moine G Bellanger L Drevet P Thai R Lajeunesse E Ménez A Léonetti M 《Vaccine》2008,26(21):2615-2626
Tat is regarded as an attractive target for the development of an AIDS vaccine. However, works suggest that Tat is a poorly immunogenic protein and therefore we attempted to increase its immunogenic potency. As we observed that Tat is highly sensitive to enzymatic degradation in vitro we tried to make it less susceptible to proteolysis using ligands. We complexed Tat101 with various sulfated sugars and observed that some of these ligands made the protein more resistant to proteolysis and more immunogenic. In a more thorough study, we observed that a low-molecular-weight heparin fragment, called Hep6000, altered both the cell-binding capacity and transactivating activity of Tat101, suggesting that this sulfated polysaccharide can make the protein less toxic. Sera raised against Tat101 and Tat101/Hep6000 similarly bound mainly to the N-terminal region of the protein, indicating that formation of the complex does not alter the B-cell immunodominant region. Anti-Tat101/Hep6000 antisera neutralized the transactivating activity of Tat101 more efficiently than anti-Tat101 antisera. Altogether, these results indicate that stabilization of Tat101 using sulfated sugars increases its immunogenicity and might be of value in increasing its vaccine efficacy. 相似文献