全文获取类型
收费全文 | 5690篇 |
免费 | 263篇 |
国内免费 | 12篇 |
专业分类
耳鼻咽喉 | 72篇 |
儿科学 | 127篇 |
妇产科学 | 112篇 |
基础医学 | 780篇 |
口腔科学 | 421篇 |
临床医学 | 411篇 |
内科学 | 1333篇 |
皮肤病学 | 92篇 |
神经病学 | 419篇 |
特种医学 | 185篇 |
外科学 | 752篇 |
综合类 | 11篇 |
预防医学 | 525篇 |
眼科学 | 55篇 |
药学 | 359篇 |
中国医学 | 52篇 |
肿瘤学 | 259篇 |
出版年
2023年 | 48篇 |
2022年 | 43篇 |
2021年 | 128篇 |
2020年 | 86篇 |
2019年 | 127篇 |
2018年 | 241篇 |
2017年 | 154篇 |
2016年 | 142篇 |
2015年 | 178篇 |
2014年 | 184篇 |
2013年 | 315篇 |
2012年 | 464篇 |
2011年 | 524篇 |
2010年 | 251篇 |
2009年 | 156篇 |
2008年 | 405篇 |
2007年 | 416篇 |
2006年 | 367篇 |
2005年 | 314篇 |
2004年 | 272篇 |
2003年 | 234篇 |
2002年 | 215篇 |
2001年 | 56篇 |
2000年 | 80篇 |
1999年 | 50篇 |
1997年 | 10篇 |
1992年 | 40篇 |
1991年 | 23篇 |
1990年 | 24篇 |
1989年 | 21篇 |
1988年 | 16篇 |
1987年 | 20篇 |
1986年 | 14篇 |
1985年 | 12篇 |
1984年 | 18篇 |
1982年 | 26篇 |
1981年 | 11篇 |
1980年 | 17篇 |
1979年 | 21篇 |
1978年 | 19篇 |
1977年 | 11篇 |
1976年 | 11篇 |
1975年 | 13篇 |
1974年 | 10篇 |
1973年 | 12篇 |
1972年 | 13篇 |
1971年 | 10篇 |
1969年 | 11篇 |
1968年 | 9篇 |
1966年 | 11篇 |
排序方式: 共有5965条查询结果,搜索用时 296 毫秒
991.
BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab 下载免费PDF全文
Sarah Huet Edith Szafer‐Glusman Bruno Tesson Luc Xerri Wayne J. Fairbrother Kiran Mukhyala Chris Bolen Elizabeth Punnoose Laurie Tonon Catherine Chassagne‐Clément Pierre Feugier Alain Viari Fabrice Jardin Gilles Salles Pierre Sujobert 《American journal of hematology》2017,92(6):515-519
BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab‐containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 patients with FL treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA‐targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over‐activation of AICDA (activation‐induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2, and BH3 functional motifs at a lower frequency than the N‐terminus and flexible loop domain, with mostly conservative aminoacid changes. With a median follow‐up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression‐free survival. 相似文献
992.
Marcia Carneiro Valera Carlos Henrique Ribeiro Camargo Cláudio Antonio Talge Carvalho Luciane Dias de Oliveira Samira Esteves Afonso Camargo Cristiana Martins Rodrigues 《Journal of applied oral science : revista FOB》2009,17(3):254-261
Objective: To evaluate the efficacy of 16% carbamide peroxide gel (CP16%), tetrahydrate sodium perborate (SP) and mixture (CP16% + SP), in walking bleaching of non-vital discolored teeth. Materials and methods: Sixty single-rooted human premolars with intact crowns were used and initial color was assessed using Vita shade guide and standardized photos. The teeth were stained using rabbit fresh blood for 18 days and photos of discolored teeth and color evaluation were performed. The teeth were divided into 4 groups (n = 15), according to bleaching agent used: G1) CP16% gel; G2) CP16% gel + SP; G3) SP + distilled water; G4: control. The bleaching agents were replaced twice at 7-day intervals for 21 days. All teeth were evaluated by two endodontists at days 0, 7, 14 and 21 and the color changes were assessed using Vita shade guide and standardized photos. The results were analyzed by Kruskal-Wallis and Dunn''s tests (p=0.05). Results: The experimental groups presented statistically similar bleaching results (p>0.05) at the end of 7, 14 and 21 days. These groups presented significantly higher bleaching efficacy than control group (G4) (p<0.05). The mixture CP16% + SP promoted return of original color in 100% of teeth at the end of 21 days. Conclusion: It was concluded that three bleaching agents were effective in bleaching of stained teeth with blood products, especially at the end of 21 days. 相似文献
993.
Marcia Carneiro Valera Katy Costa Godinho da Silva Lilian Eiko Maekawa Cláudio Antonio Talge Carvalho Cristiane Yumi Koga-Ito Carlos Henrique Ribeiro Camargo Raphael Silva e Lima 《Journal of applied oral science : revista FOB》2009,17(6):555-559
Objective:
The purpose of this study was to evaluate the action of sodium hypochlorite (NaOCl) associated with an intracanal medication against Candida albicans and Enterococcus faecalis inoculated in root canals.Material and Methods:
Thirty-six human single-rooted teeth with single root canals were used. The canals were contaminated with C. albicans and E. faecalis for 21 days and were then instrumented with 1% NaOCl. The roots were divided into 3 groups (n=12) according to the intracanal medication applied: calcium hydroxide paste, 2% chlorhexidine (CHX) gel, and 2% CHX gel associated with calcium hydroxide. The following collections were made from the root canals: a) initial sample (IS): 21 days after contamination (control), b) S1: after instrumentation, c) S2: 14 days after intracanal medication placement; S3: 7 days after intracanal medication removal. The results were analyzed statistically by the Kruskal-Wallis test at 5% significance level.Results and Conclusions:
Both 1% NaOCl irrigation and the intracanal medications were effective in eliminating E. faecalis and C. albicans inoculated in root canals. 相似文献994.
Mandeau A Aries MF Boé JF Brenk M Crebassa-Trigueros V Vaissière C Teysseyre V Bieber T 《Planta medica》2011,77(9):900-906
Owing to their high content of flavonoids and saponins, plantlets of Avena sativa L. (Poaceae) are likely to possess anti-inflammatory and immunoregulatory properties of value in the treatment of atopic dermatitis (AD). With a view to its potential use in atopic subjects at risk of developing sensitisation to dietary proteins, we prepared a plantlet extract without proteins and isolated 2 flavonoids, isoorientin-2'- O-arabinoside (1) and isovitexin-2'- O-arabinoside (2), and two saponins, avenacosides A (3) and B (4). The absence of protein in this extract was evidenced by electrophoresis and Western immunoblotting. Furthermore, Western immunoblotting demonstrated the absence of cross-reaction between grain and plantlet proteins. We evaluated the anti-inflammatory activity of the plantlet extract and its compounds IN VITRO in a model of keratinocyte inflammation: 6-keto prostaglandin F1 α production was inhibited by the plantlet extract (-?35?% and -?57?% at 10 and 30?μg/mL, respectively; p?0.001) and isoorientin-2'- O-arabinoside (-?31?%, -?51?%, and -?56?% at 3, 10, and 30?μg/mL, respectively; p?0.001). Intracellular interleukin-2 production in activated T lymphocytes was also inhibited by 16?%, 27?%, and 31?% with 3, 10, and 30?μg/mL plantlet extract, respectively, and by 23?% and 32?% with 3 and 10?μg/mL avenacoside A, respectively, (p?0.001), demonstrating their immunoregulatory activity IN VITRO. The plantlet extract was also effective on the phenotype and function of dendritic cells (DC) differentiated from monocytes. It decreased the expression of major histocompatibility complex class II molecules on DC and significantly impaired their stimulatory activity on autologous T-cell proliferation (-25?%, p?0.05). In conclusion, this protein-free oat plantlet extract exhibits anti-inflammatory and immunoregulatory activities in vitro. 相似文献
995.
Souto-Maior FN de Carvalho FL de Morais LC Netto SM de Sousa DP de Almeida RN 《Pharmacology, biochemistry, and behavior》2011,100(2):259-263
Linalool oxide is a monoterpene that is found in some species of aromatic plants. The effects of the inhalation of linalool oxide (0.65%, 1.25%, 2.5% and 5.0% w/w) in the elevated plus-maze and light/dark box tests as animal models of anxiety were investigated in adult male mice and compared with the effects of the reference anxiolytic diazepam (0.5 and 2.0 mg/kg), administered intraperitoneally. Additionally, the effects of inhaled linalool oxide were investigated in the rotarod test. Linalool oxide significantly increased the number of visits to the open arms of the elevated plus-maze and the amount of time spent there as well as the total number of entries. In the light/dark box test, inhalation of linalool oxide led to an increase in the time spent by the mice in the brightly-lit chamber and in the number of times the animal crossed from one compartment to another. Performance on the rotarod was unaffected. Thus, inhaled linalool oxide was found to have anxiolytic properties in both animal models, without causing any motor deficit. These results suggest that inhalation of linalool oxide may be a useful means of counteracting anxiety. 相似文献
996.
Vieira-Júnior GM Dutra LA Ferreira PM de Moraes MO Costa Lotufo LV Pessoa Cdo Ó Torres RB Boralle N Bolzani Vda S Cavalheiro AJ 《Journal of natural products》2011,74(4):776-781
Four new clerodane diterpenes, casearupestrins A-D (1-4), were isolated from the leaves of Casearia rupestris. Compounds 1 and 4 were acetylated to yield 2,7-di-O-acetylcasearupestrin A (5) and 2,6-di-O-acetylcasearupestrin D (6). All compounds were evaluated for cytotoxicity against a small panel of human cancer cell lines. Casearupestrin A (1) exhibited the most potent activity against MDA/MB-435 (human melanoma) and SF-295 (human glioblastoma) cells, superior to that of the standard drug doxorubicin. 相似文献
997.
Clézardin P 《Bulletin du cancer》2011,98(7):837-846
Bone homeostasis is maintained by the remodelling of bone which depends on a balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Malignant bone lesions are very common in patients with cancer; whether they result from a tumor in bone (giant cell tumour of bone, osteosarcoma, multiple myeloma...) or they are bony metastases from advanced cancers of which the most osteotropic are breast and prostate cancer. Malignant cells within the bone disrupt the normal bone remodelling process, leading to increased bone destruction and occurence of pathological fractures. Receptor activator of NF-kB (RANK) and its ligand (RANKL) play a pivotal role in the regulation of bone remodelling; by binding to RANK, RANKL stimulates osteoclastogenesis and bone resorption, whereas its cognate decoy receptor osteoprotegerin (OPG) blocks this process by interacting with RANKL. Tumour cells produce different factors that manipulate the RANK/RANKL/OPG pathway in order to stimulate bone destruction. Furthermore, pending on the tumour type, RANKL plays a role in the migration, invasion and proliferation of malignant cells within the bone, while OPG increases survival of tumour cells. Inhibition of RANK/RANKL system may therefore offer new therapeutic perspectives for the treatment of primitive and secondary bone cancers. 相似文献
998.
Benzaïd I Mönkkönen H Stresing V Bonnelye E Green J Mönkkönen J Touraine JL Clézardin P 《Cancer research》2011,71(13):4562-4572
The nitrogen-containing bisphosphonate zoledronic acid (ZOL), a potent inhibitor of farnesyl pyrophosphate synthase, blocks the mevalonate pathway, leading to intracellular accumulation of isopentenyl pyrophosphate/triphosphoric acid I-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester (IPP/ApppI) mevalonate metabolites. IPP/ApppI accumulation in ZOL-treated cancer cells may be recognized by Vγ9Vδ2 T cells as tumor phosphoantigens in vitro. However, the significance of these findings in vivo remains largely unknown. In this study, we investigated the correlation between the anticancer activities of Vγ9Vδ2 T cells and the intracellular IPP/ApppI levels in ZOL-treated breast cancer cells in vitro and in vivo. We found marked differences in IPP/ApppI production among different human breast cancer cell lines post-ZOL treatment. Coculture with purified human Vγ9Vδ2 T cells led to IPP/ApppI-dependent near-complete killing of ZOL-treated breast cancer cells. In ZOL-treated mice bearing subcutaneous breast cancer xenografts, Vγ9Vδ2 T cells infiltrated and inhibited growth of tumors that produced high IPP/ApppI levels, but not those expressing low IPP/ApppI levels. Moreover, IPP/ApppI not only accumulated in cancer cells but it was also secreted, promoting Vγ9Vδ2 T-cell chemotaxis to the tumor. Without Vγ9Vδ2 T-cell expansion, ZOL did not inhibit tumor growth. These findings suggest that cancers-producing high IPP/ApppI levels after ZOL treatment are most likely to benefit from Vγ9Vδ2 T-cell-mediated immunotherapy. 相似文献
999.
Schultz-Thater E Piscuoglio S Iezzi G Le Magnen C Zajac P Carafa V Terracciano L Tornillo L Spagnoli GC 《International journal of cancer. Journal international du cancer》2011,129(5):1137-1148
MAGE-A10 is a highly immunogenic member of the MAGE-A family of cancer/testis tumor-associated antigens (C/T TAAs). Studies performed with broadly reactive antibodies have helped to initially characterize this TAA. However, no specific reagents have been developed so far, thus preventing a thorough analysis of its expression in healthy and tumoral tissues. We have produced MAGE-A10 gene product in soluble recombinant form, and we have used it to generate specific monoclonal antibodies (mAbs). One of these reagents, recognizing an epitope located at the COOH terminus of the MAGE-A10 gene product, was used to stain a multitumor tissue microarray comprising more than 2,500 paraffin-embedded specimens including healthy tissues, benign tumors and malignancies of different histological origin. MAGE-A10 protein was identified as an intranuclear protein of an apparent molecular weight of 70 kDa, expressed in normal spermatogonia and spermatocytes but in no other healthy tissue. Most importantly, this C/T TAA appears to be expressed in high (>50%) percentages of cancer cells from a number of malignancies, including lung, skin and urothelial tumors. Unexpectedly, high expression of MAGE-A10 TAA at the protein level was also detectable in gynecological malignancies and stomach and gall bladder cancers. The characterization of MAGE-A10-specific reagents might set the stage for the development of targeted active immunotherapy by clarifying potential indications and by allowing the selection of patients eligible for treatment and the monitoring of its effectiveness. 相似文献
1000.
Pez F Dayan F Durivault J Kaniewski B Aimond G Le Provost GS Deux B Clézardin P Sommer P Pouysségur J Reynaud C 《Cancer research》2011,71(5):1647-1657