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11.
目的:结合免疫治疗与化疗,以改善肿瘤的治疗效果,为安全有效的肿瘤免疫治疗策略的发展提供更多见解。方法:使用工程化纳米囊泡,囊泡膜上表达PD-1受体,可以靶向肿瘤细胞表面的PD-L1,通过破坏PD-1/PD-L1免疫抑制通路增强抗肿瘤反应。同时,囊泡包裹的化疗药物阿霉素可以进入肿瘤细胞核,抑制DNA与RNA的合成,诱导肿瘤细胞死亡。结果:实验证实,制备的PD1-阿霉素材料具备良好的稳定性、安全性,能准确靶向肿瘤部位,阿霉素在细胞核部位起作用,能有效地进行肿瘤杀伤。结论:本研究首次将PD-1免疫检查点抑制与化疗药物阿霉素相结合,利用PD-1囊泡安全性高、长循环的特点作为包裹化疗药物阿霉素的载体,这种方法可以进行肿瘤细胞的有效靶向与治疗,实现肿瘤的有效清除。 相似文献
12.
兔骨髓基质干细胞复合珊瑚修复兔骨缺损的实验研究 总被引:2,自引:0,他引:2
目的:对天然珊瑚(natural coral,NC)的细胞相容性进行研究,观察其与兔骨髓基质干细胞(bone marrow stem cells.BMSCs)复合后修复兔桡骨缺损的能力。方法:从兔股骨转子窝抽取骨髓,体外培养扩增,将其接种于珊瑚上,一组分别于1、3、7、14天取材,扫描电镜(SEM)观察细胞在支架上的生长情况,另一组进行诱导,培养5天后接种于兔桡骨1cm缺损中.以珊瑚填充桡骨缺损组作为对照。结果:从第1天开始,珊瑚表面即有细胞贴壁,随时间延长,细胞数量增多,到14天时有大量胶原形成。种植于兔桡骨缺损者4周时珊瑚降解不明显,骨组织形成较少,8周时见珊瑚部分降解.骨组织形成较多,20周时珊瑚完全降解,骨折愈合。结论:BMSCs与NC复合可构建组织工程骨,能修复骨缺损,并具有成骨可靠、来源广泛、成本低廉等特点. 相似文献
13.
Despite the enormous success of combined anti-retroviral therapy, HIV infection is still a lifelong disease and continues to spread rapidly worldwide. There is a pressing need to develop a treatment that will cure HIV infection. Recent progress in stem cell manipulation and advancements in humanized mouse models have allowed rapid developments of gene therapy for HIV treatment. In this review, we will discuss two aspects of HIV gene therapy using human hematopoietic stem cells. The first is to generate immune systems resistant to HIV infection while the second strategy involves enhancing anti-HIV immunity to eliminate HIV infected cells. 相似文献
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《Journal of pharmaceutical sciences》2019,108(7):2207-2237
This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics. 相似文献
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17.
Neil E. Hoffman 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(22)
In keeping with the directive in Executive Order 13874 (Modernizing the Regulatory Framework for Agricultural Biotechnology Products) to adopt regulatory approaches that are proportionate to risk and avoid arbitrary distinctions across like products, the US Department of Agriculture (USDA) revised its biotechnology regulations by promulgating the Sustainable, Ecological, Consistent, Uniform, Responsible, and Efficient (SECURE) rule. Specifically, the SECURE rule 1) establishes exemptions for plants modified by genetic engineering where the modification could otherwise have been made through conventional breeding, 2) uses risk posed by the introduced trait to determine whether an organism is regulated, rather than relying on whether the organism was developed using a plant pest, and 3) provides a mechanism for a rapid initial review to efficiently distinguish plants developed using genetic engineering that do not pose plausible pathways to increased plant pest risk from those that do. As a result of the focused oversight on potentially riskier crops developed using genetic engineering, USDA is expected to improve the efficiency and effectiveness of its oversight program. The reduced regulatory burden is expected to promote innovation by expanding the number and diversity of developers to include smaller businesses and academics and to increase the number and variety of traits being developed through biotechnology. 相似文献
18.
Sequential hydrophile and lipophile solubilization as an efficient method for decellularization of porcine aortic valve leaflets: Structure,mechanical property and biocompatibility study
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Wei‐hua Qiao Peng Liu Dan Hu Mahmoud Al Shirbini Xian‐ming Zhou Nian‐guo Dong 《Journal of tissue engineering and regenerative medicine》2018,12(2):e828-e840
Antigenicity of xenogeneic tissues is the major obstacle to increased use of these materials in clinical medicine. Residual xenoantigens in decellularized tissue elicit the immune response after implantation, causing graft failure. With this in mind, the potential use is proposed of three protein solubilization‐based protocols for porcine aortic valve leaflets decellularization. It was demonstrated that hydrophile solubilization alone achieved incomplete decellularization; lipophile solubilization alone (LSA) completely removed all cells and two most critical xenoantigens – galactose‐α(1,3)‐galactose (α‐Gal) and major histocompatibility complex I (MHC I) – but caused severe alterations of the structure and mechanical properties; sequential hydrophile and lipophile solubilization (SHLS) resulted in a complete removal of cells, α‐Gal and MHC I, and good preservation of the structure and mechanical properties. In contrast, a previously reported method using Triton X‐100, sodium deoxycholate and IGEPAL CA‐630 resulted in a complete removal of all cells and MHC I, but with remaining α‐Gal epitope. LSA‐ and SHLS‐treated leaflets showed significantly reduced leucocyte activation (polymorphonuclear elastase) upon interaction with human blood in vitro. When implanted subdermally in rats for 6 weeks, LSA‐ or SHLS‐treated leaflets were presented with more biocompatible implants and all four decellularized leaflets were highly resistant to calcification. These findings illustrate that the SHLS protocol could be considered as a promising decellularization method for the decellularization of xenogeneic tissues in tissue engineering and regenerative medicine. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
19.
《Vaccine》2015,33(41):5386-5395
The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F1 male mice expressing human PSA and HLA-DRB1*1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV–PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP–PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV–PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8 T cells (19.6 ± 7.4%) produced IFNγ in response to the immunodominant peptide PSA65–73. In the blood of vaccinated mice, 18.4 ± 4.1% of CD8 T cells were PSA-specific as determined by the staining with H-2Db/PSA65–73 dextramers. VLPV–PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8+ T cell infiltration. Tumor growth in VLPV–PSA vaccinated mice was significantly delayed at early time points (p = 0.002, Gehan–Breslow test). Our data suggest that TC-83-based VLPV–PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV–PSA vaccine will undergo further testing for the immunotherapy of prostate cancer. 相似文献
20.
Pig kidney graft survival in a baboon for 136 days: longest life‐supporting organ graft survival to date
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Martin Wijkstrom Huidong Zhou Jagjit Singh Hidetaka Hara Mohamed Ezzelarab Cassandra Long Edwin Klein Robert Wagner Carol Phelps David Ayares Ron Shapiro Abhinav Humar David K. C. Cooper 《Xenotransplantation》2015,22(4):302-309
The longest survival of a non‐human primate with a life‐supporting kidney graft to date has been 90 days, although graft survival > 30 days has been unusual. A baboon received a kidney graft from an α‐1,3‐galactosyltransferase gene‐knockout pig transgenic for two human complement‐regulatory proteins and three human coagulation‐regulatory proteins (although only one was expressed in the kidney). Immunosuppressive therapy was with ATG+anti‐CD20mAb (induction) and anti‐CD40mAb+rapamycin+corticosteroids (maintenance). Anti‐TNF‐α and anti‐IL‐6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6 to 1.6 mg/dl) until termination. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein‐losing nephropathy were observed. There was no evidence of an elicited anti‐pig antibody response. Death was from septic shock (Myroides spp). Histology of a biopsy on day 103 was normal, but by day 136, the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti‐inflammatory agents prevented immune injury and a protein‐losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality. 相似文献