全文获取类型
收费全文 | 123篇 |
免费 | 20篇 |
专业分类
儿科学 | 3篇 |
基础医学 | 16篇 |
口腔科学 | 3篇 |
临床医学 | 16篇 |
内科学 | 26篇 |
皮肤病学 | 8篇 |
神经病学 | 5篇 |
特种医学 | 1篇 |
外科学 | 31篇 |
综合类 | 2篇 |
预防医学 | 5篇 |
药学 | 12篇 |
中国医学 | 2篇 |
肿瘤学 | 13篇 |
出版年
2023年 | 2篇 |
2022年 | 6篇 |
2021年 | 16篇 |
2020年 | 11篇 |
2019年 | 12篇 |
2018年 | 11篇 |
2017年 | 6篇 |
2016年 | 10篇 |
2015年 | 6篇 |
2014年 | 6篇 |
2013年 | 6篇 |
2012年 | 12篇 |
2011年 | 3篇 |
2010年 | 4篇 |
2009年 | 2篇 |
2008年 | 3篇 |
2007年 | 3篇 |
2006年 | 2篇 |
2005年 | 2篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1992年 | 1篇 |
排序方式: 共有143条查询结果,搜索用时 15 毫秒
101.
102.
Regional,but not systemic recruitment/expansion of dendritic cells by a pluronic-formulated Flt3-ligand plasmid with vaccine adjuvant activity 总被引:9,自引:0,他引:9
Sang H Pisarev VM Munger C Robinson S Chavez J Hatcher L Parajuli P Guo Y Talmadge JE 《Vaccine》2003,21(21-22):3019-3029
Regional recruitment of dendritic cells (DCs) by the local administration of granulocyte macrophage-colony stimulating factor (GM-CSF) or Flt3-ligand (Flt3L) has vaccine adjuvant activity. However, Flt3L, with its DC growth factor activity, has not been extensively studied as a vaccine adjuvant, particularly as a plasmid vector. We report that the intramuscular (IM) injection of a Flt3L plasmid (pNGVL-hFlex), when formulated in a pluronic carrier (SP1017, Supratek Pharma, Inc., Laval, Que., Canada), recruits DC to the injection site and regional lymph nodes (LNs) and augments immune responses to a p17 HIV plasmid vaccine to a greater extent than the injection of a naked DNA vaccine alone. Following IM administration of pNGVL-hFlex, Flt3L mRNA, Flt3L protein and infiltrating DC accumulate at the injection site. The number of DC in the draining LNs are also significantly increased with the greatest increase observed following injection of 2.5 microg of pNGVL-hFlex formulated in 0.01% SP1017. Flow cytometric studies demonstrate that the LN-infiltrating DC is mainly of the CD11c(+)CD11b(-) phenotype (IL-12 producing). Further, the co-injection of pNGVL3-hFlex and p17 HIV plasmids, formulated in SP1017, significantly increases the immune responses to the plasmid vaccine (pVAX-gag). The co-injection of pVAX-gag and pNGVL3-hFlex, formulated in SP1017, significantly increase delayed-type hypersensitivity responses and the numbers of antigen (Ag)-specific interferon-gamma secreting T cells in the spleen (Enzyme Linked Immune Spot (ELISpot) assay), compared to mice immunized with pVAX-gag formulated in SP1017 alone. We conclude that the IM injection of pNGVL-hFlex with SP1017 can increase the number of DC in draining LN and at the site of injection, thereby providing adjuvant activity for a plasmid vaccine resulting in a significantly increased, Ag-specific T cell response. 相似文献
103.
104.
Sandesh Parajuli Patrick K. Reville Thomas M. Ellis Arjang Djamali Didier A. Mandelbrot 《American journal of transplantation》2017,17(12):3210-3218
There is limited information about the role of protocol kidney biopsies for de novo donor‐specific antibodies (dnDSA) in kidney transplant recipients, especially in those with stable graft function. We initiated a routine posttransplant DSA monitoring and surveillance biopsy program for dnDSA since 2014. We identified 45 kidney transplant recipients with dnDSA detected between January 2014 and February 2017 who underwent kidney biopsy within 60 days of detection of dnDSA. Twenty‐nine (64%) had stable graft function and 16 (36%) had impaired graft function at the time of dnDSA detection. Even in the group with stable graft function, we found a high rate of rejection (53%) on biopsy. Eighty‐eight percent of patients with impaired graft function had rejection. Those patients with impaired graft function had significantly lower estimated glomerular filtration rate at 12 months postbiopsy and at last follow‐up. Those with impaired graft function had more graft failures; however, this result was not statistically significant. The high rate of asymptomatic rejection, and the fact that outcomes in asymptomatic patients are poor, is in support of the utility of surveillance biopsies in patients with dnDSA. 相似文献
105.
106.
Cytolysis of human dendritic cells by autologous lymphokine-activated killer cells: participation of both T cells and NK cells in the killing. 总被引:3,自引:0,他引:3
P Parajuli Y Nishioka N Nishimura S M Singh M Hanibuchi H Nokihara H Yanagawa S Sone 《Journal of leukocyte biology》1999,65(6):764-770
Dendritic cells (DC) play a key role in the initiation of immune response by stimulating the naive T cells. The fate of DC after the initiation of immune response is not clearly understood. Although there are few reports implicating natural killer (NK) cells in the elimination of DC, killing of DC by LAK cells, and specifically by T cells, has not been studied. In this study, we observed that DC, generated from monocytes, in vitro in the presence of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and tumor necrosis factor alpha were susceptible to cytolysis by lymphokine-activated killer (LAK) cells induced in the presence of IL-2 and IL-15 but not IL-12 alone. However, LAK cells induced by a combination of IL-12 and suboptimal dose of IL-2 were cytotoxic to DC. When purified lymphocytes were activated with IL-2, the CD8+/CD57- fraction (T-LAK), but not the CD8-/CD57+ fraction (NK-LAK) was cytotoxic to autologous DC. However, when unseparated peripheral blood mononuclear cells were used to generate LAK cells, both T-LAK and NK-LAK fractions showed equal cytotoxicity against autologous DC. Monoclonal antibodies against CD54, CD11a, and CD18 significantly inhibited the cytolysis, indicating that the killing involves the engagement of CD54 with its ligands. 相似文献
107.
Anup Adhikari Bibek Raj Bhattarai Ashika Aryal Niru Thapa Puja KC Ashma Adhikari Sushila Maharjan Prem B. Chanda Bishnu P. Regmi Niranjan Parajuli 《RSC advances》2021,11(60):38126
Unnatural amino acids have gained significant attention in protein engineering and drug discovery as they allow the evolution of proteins with enhanced stability and activity. The incorporation of unnatural amino acids into proteins offers a rational approach to engineer enzymes for designing efficient biocatalysts that exhibit versatile physicochemical properties and biological functions. This review highlights the biological and synthetic routes of unnatural amino acids to yield a modified protein with altered functionality and their incorporation methods. Unnatural amino acids offer a wide array of applications such as antibody-drug conjugates, probes for change in protein conformation and structure–activity relationships, peptide-based imaging, antimicrobial activities, etc. Besides their emerging applications in fundamental and applied science, systemic research is necessary to explore unnatural amino acids with novel side chains that can address the limitations of natural amino acids.Incorporation of unnatural amino acids into protein offers wide array of applications in fundamental and applied science. 相似文献
108.
The inflammatory cytokines interleukin (IL)-10 and tumor necrosis factor (TNF)-α play an important role in left ventricular (LV) remodeling after myocardial infarction (MI). Phosphatase and tensin homolog
deleted on chromosome ten (PTEN) inactivates protein kinase Akt and promotes cell death in the heart. However, it is not known
whether PTEN promotes post-MI remodeling by regulating IL-10 and TNF-α. MI was induced in wild-type (WT) mice and Pten heterozygous mutant (HET) mice. Pten adenoviruses (adPten) or empty vectors (adNull) were injected into the peri-infarct area of WT mice. LV dilation was attenuated and fractional shortening was increased
in HET mice compared to WT mice. Survival rate and fractional shortening were decreased in adPten mice compared to adNull mice. Leukocyte infiltration into the peri-infarct area was attenuated in HET mice and worsened in adPten mice. PTEN expression was upregulated in the infarcted heart of WT mice. Partial inactivation of PTEN increased the production
of IL-10 and decreased the expression of TNF-α and matrix metalloproteinase (MMP)-2 and -9 after MI in HET mice. PTEN overexpression caused opposite effects in the infarcted
heart. Moreover in the infarcted heart of HET mice, Akt inhibition decreased Stat3 phosphorylation and IL-10 expression, and
blockade of the IL-10 receptor increased TNF-α and MMP-2 expression. Both Akt inhibition and IL-10 receptor blockade abolished the attenuation of post-MI remodeling in
HET mice. In conclusion, PTEN is critically involved in post-MI remodeling through the Akt/IL-10 signaling pathway. Therefore,
targeting PTEN may be an effective approach to post-MI remodeling. 相似文献
109.
Yosuke Danjo Eiji Shigetomi Yukiho J. Hirayama Kenji Kobayashi Tatsuya Ishikawa Yugo Fukazawa Keisuke Shibata Kenta Takanashi Bijay Parajuli Youichi Shinozaki Sun Kwang Kim Junichi Nabekura Schuichi Koizumi 《The Journal of experimental medicine》2022,219(4)
Activation of astrocytes has a profound effect on brain plasticity and is critical for the pathophysiology of several neurological disorders including neuropathic pain. Here, we show that metabotropic glutamate receptor 5 (mGluR5), which reemerges in astrocytes in a restricted time frame, is essential for these functions. Although mGluR5 is absent in healthy adult astrocytes, it transiently reemerges in astrocytes of the somatosensory cortex (S1). During a limited spatiotemporal time frame, astrocytic mGluR5 drives Ca2+ signals; upregulates multiple synaptogenic molecules such as Thrombospondin-1, Glypican-4, and Hevin; causes excess excitatory synaptogenesis; and produces persistent alteration of S1 neuronal activity, leading to mechanical allodynia. All of these events were abolished by the astrocyte-specific deletion of mGluR5. Astrocytes dynamically control synaptic plasticity by turning on and off a single molecule, mGluR5, which defines subsequent persistent brain functions, especially under pathological conditions. 相似文献
110.