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101.
Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles
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Skountzou I Quan FS Gangadhara S Ye L Vzorov A Selvaraj P Jacob J Compans RW Kang SM 《Journal of virology》2007,81(3):1083-1094
The rapid worldwide spread of human immunodeficiency virus (HIV) mandates the development of successful vaccination strategies. Since live attenuated HIV is not accepted as a vaccine due to safety concerns, virus-like particles (VLPs) offer an attractive safe alternative because they lack the viral genome yet they are perceived by the immune system as a virus particle. We hypothesized that adding immunostimulatory signals to VLPs would enhance their efficacy. To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo. Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF. In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4(+)- and CD8(+)-T-cell responses to SIV Env, compared to standard SIV VLPs. Taken together, these results demonstrate that the incorporation of immunostimulatory molecules enhances humoral and cellular immune responses. We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens. 相似文献
102.
Tumor cells can be modified to express immunostimulatory molecules such as B7-1 by protein transfer using purified glycosylphosphatidylinositol-anchored B7-1 (GPI-B7-1). In this study recombinant baculovirus encoding GPI-B7-1 (vBacB7-1(GPI)) was established to obtain large quantities of purified GPI-B7-1 to modify tumor cells by protein transfer. vBacB7-1(GPI)-infected insect cells showed high-level cell surface expression of GPI-B7-1 that was susceptible to PIPLC treatment. GPI-B7-1 expressed in insect cells (Bac-GPI-B7-1) mediated T cell proliferation, indicating that the GPI-B7-1 retains costimulatory activity. Moreover, Bac-GPI-B7-1 was completely solubilized in Triton X-100 at 4 degrees C compared to 22% solubilization of GPI-B7-1 expressed in CHOK1 cells, suggesting that GPI-anchored proteins expressed in insect cells may not be clustered into the detergent-insoluble fraction. SDS-PAGE analysis of Bac-GPI-B7-1 showed faster mobility (45 kDa) compared to GPI-B7-1 from CHOK1 (68 kDa) and this difference may be due to a difference in glycosylation. Cell binding assays showed that immunoaffinity-purified Bac-GPI-B7-1 retained its functional ability to bind CD28(+) cells. Moreover, when human tumor cells were incubated with this functionally active purified GPI-B7-1, an efficient transfer of B7-1 onto tumor cells was observed. These results demonstrate that GPI-B7-1 can be expressed in insect cells in a functionally active form and can be used to modify tumor cells for immunotherapeutic applications. 相似文献
103.
Relationships between antigen-specific helper and inducer suppressor T cell hybridomas 总被引:5,自引:0,他引:5
V K Kuchroo J K Steele R M O'Hara S Jayaraman P Selvaraj E Greenfield R T Kubo M E Dorf 《Journal of immunology (Baltimore, Md. : 1950)》1990,145(2):438-448
Ts1, or inducer suppressor T cells, share many phenotypic and functional characteristics with helper/inducer subset of T cells. In order to evaluate the relationship between these cell types, we made a series of new Ts1 hybridomas by the fusion of Ts1 cells with the functionally TCR alpha/beta-negative BW thymoma (BW 1100). Three Ts1 hybridomas (CKB-Ts1-38, CKB-Ts1-53, and CKB-Ts1-81) were established that express TCR and produce Ag-specific suppressor factors constitutively, thus making it possible to study the nature and specificity of Ag receptors, MHC restriction, and lymphokine production by the Ts1 hybridomas. Results presented in this report demonstrate that all the Ts1 hybridomas described here express CD3-associated TCR-alpha beta. These three Ts1 hybridomas recognize Ag (NP-KLH) specifically in a growth inhibition assay and this recognition is restricted by IE molecules. Two of the hybridomas also produce IL-2 or IL-2 and IL-4 upon Ag-specific activation. Thus, by these three criteria the Ts1 hybridomas appear indistinguishable from Th cells. These three Ts1 hybridomas, however, release suppressor factors (TsF1) in the supernatant that suppress both in vivo DTH and in vitro PFC responses in an Ag-specific manner. Like the TsF1 factors characterized previously, the suppression mediated by these factors are Igh restricted and lack H-2 restriction. These factors mediate suppression when given in the induction phase but not during the effector phase of the immune response. The TsF1 factors are absorbed by Ag (NP-BSA), and anti-TCR affinity columns and the suppressor activity can be recovered by elution. The data are consistent with the interpretation that Ts1 inducer-suppressor T cells are related to Th cells; the feature that distinguishes these cells is the ability to produce Ag-binding factors that specifically suppress immune responses. 相似文献
104.
pIJ1008, a Rhizobium leguminosarum plasmid which determines hydrogen uptake ability and symbiotic functions in pea was transferable to three of seven natural isolates of R. meliloti tested. In these three strains, pIJ1008 was maintained stably with the respective sym megaplasmid indigenous to each R. meliloti strain. These strains carrying both plasmids nodulated alfalfa but not pea. By reisolation and examination of the strains from alfalfa nodule tissue, it was shown that pIJ1008 continued to be maintained but that pea-nodulation ability was suppressed.In one strain of R. meliloti which carries a 200 kb cryptic plasmid (in addition to a megaplasmid), the transfer and selection for pIJ1008 resulted in the loss of the cryptic plasmid.In three separate plant growth experiments, alfalfa nodules induced by each of the R. meliloti strain carrying both sym plasmids were assayed for hydrogen uptake activity. The average activity was 40-, 3.5-and 2-fold higher than with the respective pIJ1008-free strains. However, this higher activity was not accompanied by an increase in plant biomass or nitrogen content of shoots.C.B.R.I. Contribution Number: 1478 相似文献
105.
106.
Prabhakaran Vasantha-Srinivasan Muthiah Chellappandian Sengottayan Senthil-Nathan Athirstam Ponsankar Annamalai Thanigaivel Sengodan Karthi Edward-Sam Edwin Selvaraj Selin-Rani Kandaswamy Kalaivani Filippo Maggi Giovanni Benelli 《Journal of Asia》2018,21(4):1466-1472
Fresh leaves of Piper betle Linn. (Piperales: Piperaceae) and Sphaeranthus indicus Linn. (Asterales: Asteraceae), commonly known as betel leaves and East Indian globe thistle, respectively, were harvested and steam distilled for the extraction of P. betle and S. indicus crude volatile oils (Pb-CVO and Si-CVO, respectively). LC50 calculated on 3rd instar larvae of dengue mosquito Aedes aegypti Linn. (Diptera: Culicidae) was 42.17?ppm for PbSi-CVO (i.e., herbal formulation based on the EOs of P. betle and S. indicus). The larval and pupal duration were significantly longer post-treatment with 100?ppm of PbSi-CVO, if compared to control. We observed that PbSi-CVO significantly altered the detoxifying enzymes GST and CYP450 compared to the expression of control. Sub-lethal concentrations of PbSi-CVO showed strong repellent properties against dengue mosquitoes, without adverse reactions on the volunteers experiencing the repellent assays. Lastly, the adulticidal activity of PbSi-CVO was studied. Overall, our study outlined that this herbal product represents a promising candidate for the development of botanical based adulticidal agents. 相似文献
107.
Arunachalam Kalaiarasi Renu Sankar Chidambaram Anusha Kandasamy Saravanan Kalyanasundaram Aarthy Selvaraj Karthic Theodore lemuel Mathuram Vilwanathan Ravikumar 《Biotechnology letters》2018,40(2):249-256
Objectives
Copper oxide nanoparticles (CuO NPs) promoting anticancer activity may be due to the regulation of various classes of histone deacetylases (HDACs).Results
Green-synthesized CuO NPs significantly arrested total HDAC level and also suppressed class I, II and IV HDACs mRNA expression in A549 cells. A549 cells treated with CuO NPs downregulated oncogenes and upregulated tumor suppressor protein expression. CuO NPs positively regulated both mitochondrial and death receptor-mediated apoptosis caspase cascade pathway in A549 cells.Conclusion
Green-synthesized CuO NPs inhibited HDAC and therefore shown apoptosis mediated anticancer activity in A549 lung cancer cell line.108.
Shomu Bohora Amit Vora Aditya Kapoor Vanita Arora Nitish Naik Raja Selvaraj Narayan Namboodiri Anil Saxena Ajay Naik Balbir Singh C. Narsimhan Mohan Nair T.S. Kler 《Indian pacing and electrophysiology journal》2018,18(6):188-192
Cardiac implantable electronic device (CIED) procedures are being done by many operators/centers and it is projected that this therapy will remarkably increase in India in the coming years. This document by IHRS, aims at guiding the Indian medical community in the appropriate use and method of implantation with emphasis on implanter training and center preparedness to deliver a safe and effective therapy to patients with cardiac rhythm disorders and heart failure. 相似文献
109.
Balaji Prakash S. Selvaraj M. R. N. Murthy Y. N. Sreerama D. Rajagopal Rao Lalitha R. Gowda 《Journal of molecular evolution》1996,42(5):560-569
Plant seeds contain a large number of protease inhibitors of animal, fungal, and bacterial origin. One of the well-studied
families of these inhibitors is the Bowman-Birk family(BBI). The BBIs from dicotyledonous seeds are 8K, double-headed proteins.
In contrast, the 8K inhibitors from monocotyledonous seeds are single headed. Monocots also have a 16K, double-headed inhibitor.
We have determined the primary structure of a Bowman-Birk inhibitor from a dicot, horsegram, by sequential edman analysis
of the intact protein and peptides derived from enzymatic and chemical cleavage. The 76-residue-long inhibitor is very similar
to that ofMacrotyloma axillare. An analysis of this inhibitor along with 26 other Bowman-Birk inhibitor domains (MW 8K) available in the SWISSPROT databank
revealed that the proteins from monocots and dicots belong to related but distinct families. Inhibitors from monocots show
larger variation in sequence. Sequence comparison shows that a crucial disulphide which connects the amino and carboxy termini
of the active site loop is lost in monocots. The loss of a reactive site in monocots seems to be correlated to this. However,
it appears that this disulphide is not absolutely essential for retention of inhibitory function. Our analysis suggests that
gene duplication leading to a 16K inhibitor in monocots has occurred, probably after the divergence of monocots and dicots,
and also after the loss of second reactive site in monocots.
S. Selvaraj is on leave from Department of Physics, Bharathidasan University, Tiruchirapalli 620 024, Tamilnadu, India
Correspondence to: M.R.N. Murthy 相似文献
110.
N. Selvaraj R. Medhamurthy S. G. Ramachandra M. R. Sairam N. R. Moudgal 《Journal of biosciences》1996,21(4):497-510
The objective of the current study was to investigate the mechanism by which the corpus luteum (CL) of the monkey undergoes
desensitization to luteinizing hormone following exposure to increasing concentration of human chorionic gonadotrophin (hCG)
as it occurs in pregnancy. Female bonnet monkeys were injected (im) increasing doses of hCG or dghCG beginning from day 6
or 12 of the luteal phase for either 10 or 4 or 2 days. The day of oestrogen surge was considered as day ‘0’ of luteal phase.
Luteal cells obtained from CL of these animals were incubated with hCG (2 and 200 pg/ml) or dbcAMP (2.5,25 and 100 M) for
3h at 37°C and progesterone secreted was estimated. Corpora lutea of normal cycling monkeys on day 10/16/22 of the luteal
phase were used as controls. In addition thein vivo response to CG and deglycosylated hCG (dghCG) was assessed by determining serum steroid profiles following their administration.
hCG (from 15–90 IU) but not dghCG (15-90 IU) treatment in vivo significantly (P < 0.05) elevated serum progesterone and oestradiol
levels. Serum progesterone, however, could not be maintained at a elevated level by continuous treatment with hCG (from day
6–15), the progesterone level declining beyond day 13 of luteal phase. Administering low doses of hCG (15-90 IU/day) from
day 6–9 or high doses (600 IU/day) on days 8 and 9 of the luteal phase resulted in significant increase (about 10-fold over
corresponding control P < 0.005) in the ability of luteal cells to synthesize progesterone (incubated controls) in vitro.
The luteal cells of the treated animals responded to dbcAMP (P < 0.05) but not to hCC added in vitro. The in vitro response
of luteal cells to added hCG was inhibited by 0,50 and 100% if the animals were injected with low (15-90 IU) or medium (100
IU) between day 6–9 of luteal phase and high (600 IU on day 8 and 9 of luteal phase) doses of dghCG respectively; such treatment
had no effect on responsivity of the cells to dbcAMP. The luteal cell responsiveness to dbcAMP in vitro was also blocked if
hCG was administered for 10 days beginning day 6 of the luteal phase. Though short term hCG treatment during late luteal phase
(from days 12—15) had no effect on luteal function, 10 day treatment beginning day 12 of luteal phase resulted in regain ofin vitro responsiveness to both hCG (P < 0.05) and dbcAMP (P < 0.05) suggesting that luteal rescue can occur even at this late stage.
In conclusion, desensitization of the CL to hCG appears to be governed by the dose/period for which it is exposed to hCG/dghCG.
That desensitization is due to receptor occupancy is brought out by the fact that (i) this can be achieved by giving a larger
dose of hCG over a 2 day period instead of a lower dose of the hormone for a longer (4 to 10 days) period and (ii) the effect
can largely be reproduced by using dghCG instead of hCG to block the receptor sites. It appears that to achieve desensitization
to dbcAMP also it is necessary to expose the luteal cell to relatively high dose of hCG for more than 4 days 相似文献