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91.
Interleukin 4 inhibition of prostaglandin E2 synthesis blocks interstitial collagenase and 92-kDa type IV collagenase/gelatinase production by human monocytes. 总被引:10,自引:0,他引:10
M L Corcoran W G Stetler-Stevenson P D Brown L M Wahl 《The Journal of biological chemistry》1992,267(1):515-519
Activation of human monocytes results in the production of interstitial collagenase through a prostaglandin E2 (PGE2)-cAMP-dependent pathway. Inasmuch as interleukin 4 (IL-4) has been shown to inhibit PGE2 synthesis by monocytes, we examined the effect of IL-4 on the production of human monocyte interstitial collagenase. Additionally, we also assessed the effect of IL-4 on the production of 92-kDa type IV collagenase/gelatinase and tissue inhibitor of metalloproteinase-1 (TIMP-1) by monocytes. The inhibition of PGE2 synthesis by IL-4 resulted in decreased interstitial collagenase protein and activity that could be restored by exogenous PGE2 or dibutyryl cyclic AMP (Bt2cAMP). IL-4 also suppressed ConA-stimulated 92-kDa type IV collagenase/gelatinase protein and zymogram enzyme activity that could be reversed by exogenous PGE2 or Bt2cAMP. Moreover, indomethacin suppressed the ConA-induced production of 92-kDa type IV collagenase/gelatinase. These data demonstrate that, like monocyte interstitial collagenase, the conA-inducible monocyte 92-kDa type IV collagenase/gelatinase is regulated through a PGE2-mediated cAMP-dependent pathway. In contrast to ConA stimulation, unstimulated monocytes released low levels of 92-kDa type IV collagenase/gelatinase that were not affected by IL-4, PGE2, or Bt2cAMP, indicating that basal production of this enzyme is PGE2-cAMP independent. IL-4 inhibition of both collagenases was not a result of increased TIMP expression since Western analysis of 28.5-kDa TIMP-1 revealed that IL-4 did not alter the increased TIMP-1 protein in response to ConA. These data indicate that IL-4 may function in natural host regulation of connective tissue damage by monocytes. 相似文献
92.
Parvovirus B19 is the causative agent of "fifth disease" of childhood. It has been implicated in a variety of conditions, including unsuccessful pregnancy and rheumatoid arthritis, and is a potential contaminant of blood products. There has been little study of immunity to parvovirus B19, and the exact nature of the protective humoral and cell-mediated immune response is unclear. Immune responses to purified virus capsid proteins, VP1 and VP2, were examined from a cohort of recently infected children and compared with responses from long-term convalescent volunteers. The results demonstrate that antibody reactivity is primarily maintained against conformational epitopes in VP1 and VP2. The unique region of VP1 appears to be a major target for cell-mediated immune responses, particularly in recently infected individuals. We confirm that antibody reactivity against linear epitopes of VP2 is lost shortly after infection but find no evidence of the proposed phenotypic switch in either the subclass of parvovirus B19-specific antibody or the pattern of cytokine production by antigen-specific T cells. The dominant subclass of specific antibody detected from both children and adults was immunoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 production by isolated lymphocytes from children or adults. In contrast, lymphocytes from convalescent adults produced a typical type 1 response associated with high levels of IL-2 and gamma interferon (IFN-gamma). However, we observed a significant (P<0.001) deficit in the production of IFN-gamma in response to VP1 or VP2 from lymphocytes isolated from children. Taken together, these results imply that future parvovirus B19 vaccines designed for children will require the use of conformationally preserved capsid proteins incorporating Th1 driving adjuvants. Furthermore, these data suggest novel mechanisms whereby parvovirus B19 infection may contribute to rheumatoid arthritis and unsuccessful pregnancy. 相似文献
93.
94.
Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses,but no correlation to viral load 总被引:24,自引:0,他引:24
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Addo MM Yu XG Rathod A Cohen D Eldridge RL Strick D Johnston MN Corcoran C Wurcel AG Fitzpatrick CA Feeney ME Rodriguez WR Basgoz N Draenert R Stone DR Brander C Goulder PJ Rosenberg ES Altfeld M Walker BD 《Journal of virology》2003,77(3):2081-2092
Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/10(6) PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8+-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8+-T-cell response, even if a comprehensive pan-genome screening approach is applied. 相似文献
95.
Chromosome size polymorphisms in Plasmodium falciparum can involve deletions and are frequent in natural parasite populations 总被引:25,自引:0,他引:25
A comparison of independent cultured isolates of Plasmodium falciparum revealed that while chromosome number was constant, the sizes of analogous chromosomes varied widely. We show here that chromosome size polymorphisms are not generated during differentiation of the asexual blood stages, as the molecular karyotype of a cloned parasite line is constant through this part of the life cycle. Experiments using whole P. falciparum chromosomes as hybridization probes to examine polymorphisms within two independent parasite populations indicate that the polymorphisms observed here are not the consequence of large-scale interchromosomal exchanges, and imply that deletions/duplications represent one mode of generating chromosome length polymorphisms. Although the deletions probably involve repetitive DNA, we show here that structural genes for P. falciparum antigens can also be lost. Furthermore, these dramatic size polymorphisms occur not only in cultured lines of P. falciparum, but with surprising frequency in natural malarial infections. 相似文献
96.
97.
Raiza Brandão Peres Asma Inam Ullah Ludmila Ferreira de Almeida Fiuza Patricia Bernardino Silva Marcos M. Batista Olivia Corcoran Tummala Rama Krishna Reddy Maria de Nazaré Correia Soeiro 《Bioorganic & medicinal chemistry letters》2018,28(11):2018-2022
Chagas disease is a neglected pathology responsible for about 12,000 deaths every year across Latin America. Although six million people are infected by the Trypanosoma cruzi, current therapeutic options are limited, highlighting the need for new drugs. Here we report the preliminary structure activity relationships of a small library of 17 novel pyridyl sulfonamide derivatives. Analogues 4 and 15 displayed significant potency against intracellular amastigotes with EC50 of 5.4?µM and 8.6?µM. In cytotoxicity assays using mice fibroblast L929 cell lines, both compounds indicated low toxicity with decent selectivity indices (SI) >36 and?>23 respectively. Hence these compounds represent good starting points for further lead optimization. 相似文献
98.
99.
Wade CE Harper JS Daunton NG Corcoran ML Morey-Holton E 《Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology》1997,4(3):43-48
To assess the effect of gravity on growth, immature rats (130-200 g) were studied during chronic altered gravity exposure and while transitioning between gravity fields. Body mass gain of rats (n = 12) exposed to 14 days of microgravity (spaceflight) was evaluated and compared to mass gain of 1 G controls. Spaceflight did not affect mass gain. Six rats exposed to 1 G following spaceflight, when compared to controls, experienced a significant (0 < 0.05) post-flight mass loss over 48 h of 13 g. Over subsequent days, however, this loss was compensated for, and no difference from 1 G controls was noted after 5 days. Exposure to hypergravity (2 G) for 16 days was evaluated [(n = 6/group): Centrifuge (C); On Center Control (OCC); Centrifuge Control (CC)]. Body mass of centrifuged and OCC rats was reduced within 24 h, with OCCs regaining control mass within 13 days. The mass difference (44 g) in centrifuged animals persisted, however, with no subsequent difference in rate of mass gain between centrifuged animals and controls over Days 3-16 (3.7 +/- 0.1 vs. 3.9 +/- 0.1 g/day, respectively). Transitioning from 2 G to 1 G resulted in a mass increase within 48 hours for centrifuged animals. Over Days 3-16 at 1 G, the rate of gain for centrifuged animals continued to increase (3.1 +/- 0.1 g/day compared to 2.1 +/- 0.1 g/day for controls); differences from control, however, were still noted on Day 16. Transitioning to an increase in a gravity field causes acute losses in body mass. In hypergravity, the acute reduction in body mass persists but the rate of mass gain is normal. Animals returning to 1 G, after acute changes, adjust to attain control mass. 相似文献
100.
MM El-Shazly El Elzayat IIA El-Sebeay YA Edmardash MM Soliman 《African Journal of Aquatic Science》2016,41(3):289-296
Manzala Lake, as one of the main Egyptian wetland ecosystems, is facing risks of pollution. An in vitro cytotoxicity test using a mammalian cell line was employed to determine the toxicity of multiple pollutants in the water and Tilapia zillii fish sampled from the lake. The concentrations of seven polychlorinated dibenzo-p-dioxins and ten polychlorinated dibenzofurans were investigated in water and muscle of the fish in 2014. Cytotoxicity testing showed that the percentage inhibition of cell viability in the studied sites ranged between 56.16% and 83.22%. Dioxin analysis indicated that the average concentrations of 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, 1,2,3,4,7,8-hexachlorodibenzofuran, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,4,6,7,8,9-octachlorodibenzofuran were higher than the toxic equivalence quotients (TEQs) set by the World Health Organization (WHO) in all water and fish muscle samples; however, the average concentration of 2,3,7,8-tetrachlorodibenzofuran was higher only in fish muscle samples. The bioaccumulation factor (BAF) ranged dramatically between 2 and 58.5 for the detected dioxins. Adverse human health effects through the consumption of fish are not expected, because dioxin levels in fish muscle are deemed safe for human consumption. Implementation of a strategic multidisciplinary action plan is strongly recommended to sustain this delta wetland ecosystem. 相似文献