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151.
Ji RR Chasalow SD Wang L Hamid O Schmidt H Cogswell J Alaparthy S Berman D Jure-Kunkel M Siemers NO Jackson JR Shahabi V 《Cancer immunology, immunotherapy : CII》2012,61(7):1019-1031
Purpose
Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, has been shown to improve overall survival in metastatic melanoma patients. As a consequence of CTLA-4 blockade, ipilimumab treatment is associated with proliferation and activation of peripheral T cells. To better understand various tumor-associated components that may influence the clinical outcome of ipilimumab treatment, gene expression profiles of tumors from patients treated with ipilimumab were characterized.Experimental design
Gene expression profiling was performed on tumor biopsies collected from 45 melanoma patients before and 3?weeks after the start of treatment in a phase II clinical trial.Results
Analysis of pre-treatment tumors indicated that patients with high baseline expression levels of immune-related genes were more likely to respond favorably to ipilimumab. Furthermore, ipilimumab appeared to induce two major changes in tumors from patients who exhibited clinical activity: genes involved in immune response showed increased expression, whereas expression of genes for melanoma-specific antigens and genes involved in cell proliferation decreased. These changes were associated with the total lymphocyte infiltrate in tumors, and there was a suggestion of association with prolonged overall survival in these patients. Many IFN-γ-inducible genes and Th1-associated markers showed increased expression after ipilimumab treatment, suggesting an accumulation of this particular type of T cell at the tumor sites, which might play an important role in mediating the antitumor activity of ipilimumab.Conclusions
These results support the proposed mechanism of action of ipilimumab, suggesting that cell-mediated immune responses play an important role in the antitumor activity of ipilimumab. 相似文献152.
Cell cycle is one of the most complex processes in the life of a dividing cell. It involves numerous regulatory proteins, which direct the cell through a specific sequence of events for the production of two daughter cells. Cyclin-dependent kinases (cdks), which complex with the cyclin proteins, are the main players in the cell cycle. They can regulate the progression of the cells through different stages regulated by several proteins including p53, p21(WAF1), p19, p16, and cdc25. Downstream targets of cyclin-cdk complexes include pRB and E2F. A cell cycle can be altered to the advantage of many viral agents, most notably polyomaviruses, papillomaviruses, adenoviruses, and retroviruses. In addition, viral protein R (Vpr) is a protein encoded by the human immunodeficiency virus type 1 (HIV-1). HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), is a member of the lentivirus class of retroviruses. This accessory protein plays an important role in the regulation of the cell cycle by causing G(2) arrest and affecting cell cycle regulators. Vpr prevents infected cells from proliferating, and collaborates with the matrix protein (MA) to enable HIV-1 to enter the nucleus of nondividing cells. Studies from different labs including ours showed that Vpr affects the functions of cell cycle proteins, including p53 and p21(WAF1). Thus, the replication of HIV-1, and ultimately its pathogenesis, are intrinsically tied to cell-cycle control. 相似文献
153.
Hamid Reza Rahimi Manoochehr Rasouli Akram Jamshidzadeh Shohreh Farshad Mehdi Saberi Firoozi Ali Reza Taghavi Simin Kiany 《Microbiology and immunology》2013,57(6):455-462
154.
Azam Mortazavifar Heidar Raissi Mahnaz Shahabi 《Journal of biomolecular structure & dynamics》2013,31(18):4852-4862
AbstractIn this study, the adsorption of Hydroxyurea (HU) onto the inner and outer surfaces of boron nitride and carbon nanotubes (CNTs) was investigated using the density functional theory calculations and molecular dynamics (MDs) simulations in aqueous solution. The values of the adsorption energy show that HU molecule is preferentially adsorbed inside of boron nitride and CNTs with the molecular axis parallel to the tubes axis, which means that the cavity of nanotubes is favorable for encapsulation of this drug. Also, it was found that the HU/boron nitride nanotube (BNNT) system is more stable than the HU/CNT system. The stability of the complexes of HU/ BNNT attributed to the formation of the intermolecular hydrogen bonds between the H atoms of HU molecule and the N atoms of BNNT, which is confirmed by Bader’s quantum theory of atoms in molecules. The natural bond orbital analysis shows the charge transfers occur from HU molecule to nanotubes in all complexes. Moreover, the adsorption of HU molecule on the surfaces of the nanotubes was investigated by explicit water models. Also, the adsorption behavior of HU on the functionalized boron nitride and CNTs is investigated to design and develop new nanocarriers for biomedical applications. Furthermore, MDs simulations are examined in the presence of one and two drug molecules. The obtained results illustrate that the lowest value of Lennard–Jones (L–J) energy between drug and nanotubes exist in the simulation system with two drug molecules. 相似文献
155.
156.
Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables with anti-inflammatory, anti-oxidant and anti-cancer activities. However, the antioxidant and anticancer mechanism of sulforaphane is not well understood. In the present research, we reported binding modes, binding constants and stability of SFN–DNA and -RNA complexes by Fourier transform infrared (FTIR) and UV–Visible spectroscopic methods. Spectroscopic evidence showed DNA intercalation with some degree of groove binding. SFN binds minor and major grooves of DNA and backbone phosphate (PO2), while RNA binding is through G, U, A bases with some degree of SFN–phosphate (PO2) interaction. Overall binding constants were estimated to be K(SFN–DNA)=3.01 (± 0.035)×104 M-1 and K(SFN–RNA)= 6.63 (±0.042)×103 M-1. At high SFN concentration (SFN/RNA = 1/1), DNA conformation changed from B to A occurred, while RNA remained in A-family structure. 相似文献
157.
Fateme Razazpour Fatemeh Gashtasbi Sima Shahabi Moshaverinia Alireza Hasannia Sadegh 《International journal of peptide research and therapeutics》2020,26(3):1629-1639
International Journal of Peptide Research and Therapeutics - One of the main challenges in oral disease is prevention of bacterial infections considering antibiotic resistance as a result of... 相似文献
158.
159.
Sheth PM Danesh A Shahabi K Rebbapragada A Kovacs C Dimayuga R Halpenny R Macdonald KS Mazzulli T Kelvin D Ostrowski M Kaul R 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(7):4789-4796
Sexual contact with HIV-infected semen is a major driving force behind the global HIV pandemic. Little is known regarding the immune correlates of virus shedding in this compartment, although HIV-1-specific CD8+ T cells are present in semen. We collected blood and semen from 27 chronically HIV-infected, therapy-naive men without common sexually transmitted infections or urethral inflammation and measured HIV-1 RNA viral load and cytokine/chemokine levels in both compartments. HIV-1 RNA levels were 10-fold higher in blood than semen, but discordantly high semen shedding was associated with higher semen levels of the proinflammatory cytokines IL-6, IL-8, IL-12, and IFN-gamma. Virus-specific CD8+ T cell epitopes were mapped in blood by IFN-gamma ELISPOT, using an overlapping HIV-1 clade B peptide matrix, and blood and semen CD8+ T cell responses were then assayed ex vivo using intracellular IFN-gamma staining. HIV-specific CD8+ responses were detected in 70% of semen samples, and their frequency was similar to or higher than blood. There was no correlation between the presence of virus-specific CD8+ T cells in semen and levels of HIV-1 RNA shedding. Among participants with detectable CD8+ IFN-gamma semen responses, their relative frequency was not associated with reduced HIV-1 RNA shedding, and their absolute number was correlated with higher levels of HIV-1 RNA semen shedding (r = 0.6; p = 0.03) and of several proinflammatory cytokines. Neither the presence nor the frequency of semen HIV-specific CD8+ T cell IFN-gamma responses in semen correlated with reduced levels of HIV RNA in semen. 相似文献
160.
Laurence M. Wood Zhen-Kun Pan Vafa Shahabi Yvonne Paterson 《Cancer immunology, immunotherapy : CII》2010,59(7):1049-1058
Tumor immunotherapy is currently at the cusp of becoming an important aspect of comprehensive cancer treatment in the clinic.
However, the need for improved adjuvants to augment immune responses against tumor antigens is always present. In this paper,
we characterize the Listeria monocytogenes-derived actin-nucleating protein, ActA, as a novel adjuvant for use in tumor immunotherapy. ActA is a virulence factor that
is expressed on the cell surface of L. monocytogenes and facilitates the production of actin tails that propel Listeria throughout the cytosol of an infected host cell. It is believed that this ActA-dependent cytosolic motility allows Listeria to evade adaptive host cell defenses and facilitates its invasion into a proximal uninfected host cell. However, there is
evidence that ActA fused to a tumor antigen and delivered by L. monocytogenes can perform a beneficial function in tumor immunotherapy as an adjuvant. Our investigation of this adjuvant activity demonstrates
that ActA, either fused to or administered as a mixture with a tumor antigen, can augment anti-tumor immune responses, break
immune tolerance and facilitate tumor eradication, which suggests that ActA is not only an effective adjuvant in tumor immunotherapy
but can also be applied in a number of therapeutic settings. 相似文献