全文获取类型
收费全文 | 102篇 |
免费 | 11篇 |
出版年
2021年 | 4篇 |
2018年 | 4篇 |
2015年 | 10篇 |
2014年 | 2篇 |
2013年 | 3篇 |
2012年 | 7篇 |
2011年 | 7篇 |
2009年 | 1篇 |
2008年 | 4篇 |
2007年 | 1篇 |
2006年 | 4篇 |
2005年 | 2篇 |
2004年 | 6篇 |
2003年 | 1篇 |
2002年 | 1篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1979年 | 3篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有113条查询结果,搜索用时 31 毫秒
61.
IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis 总被引:7,自引:0,他引:7
Thakker P Leach MW Kuang W Benoit SE Leonard JP Marusic S 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(4):2589-2598
Experimental autoimmune encephalomyelitis (EAE), a T cell-mediated inflammatory disease of the CNS, is a rodent model of human multiple sclerosis. IL-23 is one of the critical cytokines in EAE development and is currently believed to be involved in the maintenance of encephalitogenic responses during the tissue damage effector phase of the disease. In this study, we show that encephalitogenic T cells from myelin oligodendrocyte glycopeptide (MOG)-immunized wild-type (WT) mice caused indistinguishable disease when adoptively transferred to WT or IL-23-deficient (p19 knockout (KO)) recipient mice, demonstrating that once encephalitogenic cells have been generated, EAE can develop in the complete absence of IL-23. Furthermore, IL-12/23 double-deficient (p35/p19 double KO) recipient mice developed EAE that was indistinguishable from WT recipients, indicating that IL-12 did not compensate for IL-23 deficiency during the effector phase of EAE. In contrast, MOG-specific T cells from p19KO mice induced EAE with delayed onset and much lower severity when transferred to WT recipient mice as compared with the EAE that was induced by cells from WT controls. MOG-specific T cells from p19KO mice were highly deficient in the production of IFN-gamma, IL-17A, and TNF, indicating that IL-23 plays a critical role in development of encephalitogenic T cells and facilitates the development of T cells toward both Th1 and Th17 pathways. 相似文献
62.
Victor G. Valcour Serena S. Spudich Napapon Sailasuta Nittaya Phanuphak Sukalaya Lerdlum James L. K. Fletcher Eugene D. M. B. Kroon Linda L. Jagodzinski Isabel E. Allen Collin L. Adams Peeriya Prueksakaew Bonnie M. Slike Joanna M. Hellmuth Jerome H. Kim Jintanat Ananworanich SEARCH /RV Study Group 《PloS one》2015,10(11)
Objective
To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+).Design
24-week randomized open-label prospective evaluation.Method
Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls.Results
At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group.Conclusions
A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART. 相似文献63.
Efficient free fatty acid production in engineered Escherichia coli strains using soybean oligosaccharides as feedstock
下载免费PDF全文
![点击此处可从《Biotechnology progress》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dan Wang Hui Wu Chandresh Thakker Jared Beyersdorf George N. Bennett Ka-Yiu San 《Biotechnology progress》2015,31(3):686-694
To be competitive with current petrochemicals, microbial synthesis of free fatty acids can be made to rely on a variety of renewable resources rather than on food carbon sources, which increase its attraction for governments and companies. Industrial waste soybean meal is an inexpensive feedstock, which contains soluble sugars such as stachyose, raffinose, sucrose, glucose, galactose, and fructose. Free fatty acids were produced in this report by introducing an acyl‐ACP carrier protein thioesterase and (3R)‐hydroxyacyl‐ACP dehydratase into E. coli. Plasmid pRU600 bearing genes involved in raffinose and sucrose metabolism was also transformed into engineered E. coli strains, which allowed more efficient utilization of these two kinds of specific oligosaccharide present in the soybean meal extract. Strain ML103 (pRU600, pXZ18Z) produced ~1.60 and 2.66 g/L of free fatty acids on sucrose and raffinose, respectively. A higher level of 2.92 g/L fatty acids was obtained on sugar mixture. The fatty acid production using hydrolysate obtained from acid or enzyme based hydrolysis was evaluated. Engineered strains just produced ~0.21 g/L of free fatty acids with soybean meal acid hydrolysate. However, a fatty acid production of 2.61 g/L with a high yield of 0.19 g/g total sugar was observed on an enzymatic hydrolysate. The results suggest that complex mixtures of oligosaccharides derived from soybean meal can serve as viable feedstock to produce free fatty acids. Enzymatic hydrolysis acts as a much more efficient treatment than acid hydrolysis to facilitate the transformation of industrial waste from soybean processing to high value added chemicals. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:686–694, 2015 相似文献
64.
Kaila N Thomas BE Thakker P Alvarez JC Camphausen RT Crommie D 《Bioorganic & medicinal chemistry letters》2001,11(2):151-155
The design and synthesis of novel beta-C-mannosides that inhibit the binding of sialyl Lewis x to E-selectin are described. Compounds that contained a phenyl substituent at the C-6 position were found to have increased potency. 相似文献
65.
Catechol-O-methyltransferase is inactivated rapidly by incubation with N-iodoacetyl-3,5-dimethoxy-4-hydroxyphenylethylamine; not by the N-acetyl analogue. Iodoacetate or iodoacetamide produce slight inactivation. Inactivation is first order with respect to enzyme activity. A kinetic analysis suggests the formation of a dissociable enzyme-inhibitor complex prior to inactivation. Substrate, 3,4-dihydroxybenzoate, protects the enzyme from alkylation and loss of activity. 相似文献
66.
We have shown earlier that metabolism of carcinogenic 6-fluorobenzo(c)-phenanthrene by liver microsomes of 3-methylcholanthrene treated rats generate K-region oxide as the major metabolite, while no K-region oxide survives in benzo(c)-phenanthrene metabolism under identical conditions. To understand the influence of fluoro group on the generation of K-region oxide from this hydrocarbon, we have determined the enantiomeric composition and absolute configuration of the metabolic 6-fluorobenzo(c)phen-anthrene-7,8-oxide. Interestingly, the microsomal cytochrome P-450c forms predominantly the 5R,6S enantiomer from B(c)Ph, while it exhibits a reversal of stereoselectivity with 6-fluorobenzo(c)phenanthrene forming predominantly the 7S,8R enantiomer. We have attributed this observation to an unfavourable interaction of the fluoro group with the hydrophobic binding pocket of the isozyme. 相似文献
67.
D R Thakker C Boehlert K L Kirk R Antkowiak C R Creveling 《The Journal of biological chemistry》1986,261(1):178-184
Selectivity of catechol O-methyltransferase has been examined for the three ring-fluorinated norepinephrines to elucidate the role of acidity of the phenolic groups in their methylation. Substitution of fluorine at the 5-position of norepinephrine reverses the selectivity of catechol O-methyltransferase so that p-O-methylation predominates. The 5-fluoro substituent also causes the pKa of the p-hydroxyl group to decrease substantially. In contrast, 2- and 6-fluoronorepinephrines are methylated predominantly at the m-hydroxyl group. These results suggest that acidity of a phenolic group can play an important role in its ability to be methylated by catechol O-methyltransferase. Percentages of p-O-methylation of norepinephrine and its fluorinated derivatives increase with pH. This relative increase in p-O-methylation appears to accompany ionization of a group with pKa of 8.6, 7.7, 7.9, and 8.4 for norepinephrine and its 2-, 5-, and 6-fluoro derivative, respectively. These pKa values are the same as or similar to the pKa values of a phenolic hydroxyl group of these substrates. 3,4-Dihydroxybenzyl alcohol and its 5-fluoro derivative are O-methylated by catechol O-methyltransferase to form p- and m-O-methyl products in approximately 1:1 and 4:1 ratios, respectively, at all pH values. Based on the above results, a catechol-binding site model for catechol O-methyltransferase is proposed in which the two phenolic hydroxyl groups of catechol substrates are postulated to be approximately equally spaced from the methyl group of the cosubstrate S-adenosylmethionine. 相似文献
68.
A metabolically engineered Escherichia coli strain SBS550MG (pHL413) was used in this study to investigate the impact of various culture operating conditions for improving
the specific succinate production rate for better final titer while maintaining the theoretical succinate yield on glucose
in multiphase fed-batch cultures. Previously, we reported that changes in the level of aeration during the cell growth phase
significantly modified gene expression profiles and metabolic fluxes in this system (Martinez et al. 2010). Based on these observations, the examination of culture conditions was mainly focused on the aerobic growth phase. It was
found that 2–5 h of low dissolved oxygen culture during the aerobic phase improves cell productivity, but pH control during
the aerobic phase was not favorable for the system. Cell viability has been identified as a major limiting factor for succinate
production. Supplementing LB medium and betaine, an anti-osmotic stress reagent, did not improve cell activity. A higher succinate
titer (537.8 mM) using the current metabolic engineering E. coli strain was achieved, which can potentially be improved further by increasing cell viability. 相似文献
69.
70.
Thakker P Marusic S Stedman NL Lee KL McKew JC Wood A Goldman SJ Leach MW Collins M Kuchroo VK Wolf SF Clark JD Hassan-Zahraee M 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(4):1986-1997
Cytosolic phospholipase A(2)α (cPLA(2)α) is the rate-limiting enzyme for release of arachidonic acid, which is converted primarily to PGs via the cyclooxygenase 1 and 2 pathways and to leukotrienes via the 5-lipoxygenase pathway. We used adoptive transfer and relapsing-remitting forms of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, in two different strains of mice (SJL or C57BL/6) to demonstrate that blockade of cPLA(2)α with a highly specific small-molecule inhibitor during the tissue-damage effector phase abrogates the clinical manifestation of disease. Using the adoptive transfer model in SJL mice, we demonstrated that the blockade of cPLA(2)α during the effector phase of disease was more efficacious in ameliorating the disease pathogenesis than the blockade of each of the downstream enzymes, cyclooxygenase-1/2 and 5-lipooxygenase. Similarly, blockade of cPLA(2)α was highly efficacious in ameliorating disease pathogenesis during the effector phase of EAE in the adoptive transfer model of EAE in C57BL/6 mice. Investigation of the mechanism of action indicates that cPLA(2)α inhibitors act on APCs to diminish their ability to induce Ag-specific effector T cell proliferation and proinflammatory cytokine production. Furthermore, cPLA(2)α inhibitors may prevent activation of CNS-resident microglia and may increase oligodendrocyte survival. Finally, in a relapsing-remitting model of EAE in SJL mice, therapeutic administration of a cPLA(2)α inhibitor, starting from the peak of disease or during remission, completely protected the mice from subsequent relapses. 相似文献