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51.
The purpose of this study was to investigate the formation of acylated impurity resulting from a chemical reaction between
the growth hormone-releasing peptide-6 (GHRP-6) and poly(lactide-co-glycolide) (PLGA) and the effect of peptide acylation
on the in vivo biological activity of GHRP-6. The peptide acylation pattern of GHRP-6 by hydrophilic PLGA polymers with different
molecular weights was characterized by reversed-phase high-performance liquid chromatography and matrix-assisted laser desorption/ionization
time-of-flight mass spectrometry. Higher levels of acylated GHRP-6 were produced with the higher molecular weight PLGA, which
might be due to the slower degradation rate of the polymer. The evaluation of the biological activity in rats showed that
the acylated GHRP-6 had a much lower activity than the intact GHRP-6. This finding suggests that the acylation reaction would
decrease the effectiveness of the GHRP-6 formulation such as PLGA microspheres. There-fore, a strategy for stabilizing the
GHRP-6 will be necessary for the development of a successful formulation of PLGA microspheres.
Published: June 8, 2007 相似文献
52.
Saleh J Cianflone K Chaudhary T Al-Riyami H Al-Abri AR Bayoumi R 《Obesity (Silver Spring, Md.)》2007,15(3):646-652
Objectives: Obesity is often associated with negative consequences, including hyperlipidemia and insulin resistance. Weight gain during pregnancy is also associated with major lipid alterations. Fat storage is enhanced in early pregnancy. At late gestation, hyperlipidemia becomes a major manifestation. The acylation‐stimulating protein (ASP) is a potent lipogenic adipocytokine that correlates with postprandial triglyceride (TG) clearance in vivo and has been linked to hyperlipidemic disorders. The role of ASP during a normal pregnancy is unknown. The objective of this study was to investigate plasma ASP levels in correlation with the lipid profile during late gestation. Research Methods and Procedures: Seventy healthy women at late gestation and 60 non‐pregnant controls of similar age and prepregnancy BMI were included in a cross‐sectional study. Fasting plasma ASP levels and the lipid profile of all of the women were measured. Results: ASP levels were markedly elevated in the pregnant women (66%, p < 0.001). ASP levels correlated strongly with the elevated levels of TGs (r = 0.608, p < 0.000), apolipoprotein B (0.519, p < 0.000), and low‐density lipoprotein‐cholesterol (r = 0.405, p < 0.000). Multivariate analysis adjusting for BMI and age showed that changes in ASP levels at late gestation were best predicted by TG and apoB levels, accounting for 53.8% of plasma ASP variation. For the controls, ASP strongly correlated with BMI, which was the only significant predictor of ASP levels. Discussion: Gestational hormone alterations during pregnancy may affect ASP function as a lipogenic factor. Increased plasma ASP levels at late gestation and their strong correlation with parameters reflecting very low‐density lipoprotein accumulation are suggestive of ASP resistance, which may further contribute to the hyperlipidemic state, shifting energy in the form of TGs to the rapidly growing fetus. 相似文献
53.
研究促酰化蛋白(acylation stimulating protein, ASP)在3T3-L1脂肪细胞分化中对脂滴相关蛋白TIP47(tail-interacting protein 47 kD)表达的影响,从而探讨ASP在成脂方面的重要意义.用免疫荧光染色法观察3T3-L1前脂肪细胞中TIP47的表达定位;采用经典激素鸡尾酒法诱导分化3T3-L1前脂肪细胞,用RT-PCR和Western 印迹方法检测诱导分化的3T3-L1脂肪细胞中TIP47 mRNA和蛋白表达;在分化过程中不同时点,对诱导分化中的3T3-L1脂肪细胞分别给予胰岛素和ASP处理,并设立相应空白对照,用RT-PCR和Western印迹方法检测TIP47 mRNA和蛋白表达. 结果显示,3T3-L1前脂肪细胞中TIP47主要在胞浆内表达;诱导分化过程中的3T3-L1脂肪细胞TIP47 mRNA和蛋白的表达水平呈时间依赖性降低;ASP对诱导分化的3T3-L1脂肪细胞中TIP47 mRNA和蛋白表达有显著的上调作用,但随着分化至48 h,其上调作用已不明显;胰岛素仅在分化的0 d对脂肪细胞中TIP47 mRNA和蛋白表达有上调作用,之后基本无影响.结果提示,ASP促成脂作用可能与其调节脂滴相关蛋白TIP47的表达密切相关,从而为认识及防治肥胖症开拓新的思路. 相似文献
54.
Trafficking of an acylated cytosolic protein: newly synthesized p56(lck) travels to the plasma membrane via the exocytic pathway
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The Src-related tyrosine kinase p56(lck) (Lck) is primarily expressed in T lymphocytes where it localizes to the cytosolic side of the plasma membrane and associates with the T cell coreceptors CD4 and CD8. As a model for acylated proteins, we studied how this localization of Lck is achieved. We followed newly synthesized Lck by pulse-chase analysis and found that membrane association of Lck starts soon after synthesis, but is not complete until at least 30-45 min later. Membrane-binding kinetics are similar in CD4/CD8-positive and CD4/CD8-negative cells. In CD4-positive T cells, the interaction with CD4 rapidly follows membrane association of Lck. Studying the route via which Lck travels from its site of synthesis to the plasma membrane, we found that: CD4 associates with Lck within 10 min of synthesis, long before CD4 has reached the plasma membrane; Lck associates with intracellular CD4 early after synthesis and with cell surface CD4 at later times; and transport of CD4-bound Lck to the plasma membrane is inhibited by Brefeldin A. These data indicate that the initial association of newly synthesized Lck with CD4, and therefore with membranes, occurs on intracellular membranes of the exocytic pathway. From this location Lck is transported to the plasma membrane. 相似文献
55.
Hyun?Gyu?ParkEmail author Jin?Hwan?Do Ho?Nam?Chang 《Biotechnology and Bioprocess Engineering》2003,8(1):1-8
With current developments in enzyme-catalyzed reactions and techniques available for rational redesign of natural biocatalysts,
the enzymatic biosynthesis can become one of the most valuable synthetic methods. Enzymatic regioselective catalysis in organic
media has played a key role in pursuing asymmetric synthesis for active chiral compounds. Here, we shortly describe some historical
issues of the rapidly growing area, enzymatic catalysis in synthetic organic chemistry and then review researches that have
been carried out in the regioselective enzymatic catalysis for the past two decades. An application of this technology to
the modification of some potential target drug compound will be also presented. 相似文献
56.
To identify and characterize small GTP-binding proteins in plant cells, GTP-binding studies were performed with electroblotted
plant proteins following SDS-polyacrylamide gel electrophoresis using [α-32P]GTP. Three species of small GTP-binding protein (21, 23, and 27 kD) which have a specific GTP-binding property were identified
in the membrane and cytosolic fractions of both monocotyledons (Zea mays) and dicotyledons (Glycine max). Moreover, these three species of small GTP-binding protein were gradually decreased when membranes were treated with hydroxylamine.
This result indicates that these small GTP-binding proteins in plant cells are fatty acylated to the membrane lipids. The
27 kDa component was partially purified from hypocotyl membranes of Glycinemax, following S-300 gel filtration, phenylsepharose CL-4B, hydroxyapatite, and Q-sepharose column chromatography. This 27 kD
protein was found to have both GTP-binding and GTPase activities. 相似文献
57.
Both hitherto unknown (+)-(R)- and (?)-(S)-thioglycidyl esters, (R)-( 2 ) and (S)-( 2 ), have been synthesized with different high enantiomeric excesses (ee) by two routes from the corresponding rac-glycidyl esters rac-( 1 ). The first includes a porcine pancreatic lipase (PPL)-mediated kinetic resolution of these esters followed by sulfuration with practically complete inversion to the (+)-(R)-enantiomer (+)-(R)-( 2 ) (36–86% ee). (?)-(S)-Thioglycidyl esters (?)-(S)-( 2 ) are obtained by the reverse reaction sequence (43–80% ee). In the latter case the hydrolysis rate is lower than that of analogous glycidyl esters. Moreover, the dependence of enantiomeric excess on the size of the acyl-group is of the opposite tendency. Therefore, in both cases suitable selection of the acid residue gives rise to maximum enantioselectivity. The irreversible lipase-catalyzed acylation of rac-glycidol and rac-thioglycidol, however, was found to be a less suitable alternative. The enantiomeric excess of recovered homochiral esters was determined by chiral chromatography using modified cellulose stationary phases (OB, OD). © 1993 Wiley-Liss, Inc. 相似文献
58.
59.
Treatment of neuropeptide Y (NPY,1) for 20 hr with a 20 equivalent excess of N-propionyl succinimide (2) in 10 mM phosphate buffer,pH 6.0, yields NPY and N-propionyl-NPY (3) as major products, and atpH 7.5 the major product is N, N-dipropionyl-NPY. However, acylation of NPY with one equivalent of N-(5-azido-2-nitrobenzolyloxy)-succinimide (5) is more rapid, yielding N-(5-azido-2-nitrobenzoyl)-NPY (6) in 70% conversion yield after only 5 min. Thus, in spite of its increased reactivity, the N-hydroxysuccinimide active ester shows enhanced- vs.-NH2 selectivity relative to2. The activities of3, 4, and6 as reversible, competitive ligands at rat brain NPY binding sites and of6 as an irreversible photoaffinity label are reported.Abbreviations used NPY
neuropeptide Y
- PYY
peptide YY
- DNFB
dinitrofluorobenzene
- DNP
dinitrophenyl
- LAPase
leucine aminopeptidase m
- HPLC
high-performance liquid chromatography
- RT
retention time
- FAB+MS
positive fast atom bombardment mass spectrometry
Taken in part from the Ph.D. dissertation of Longqin Hu, The University of Kansas, 1993. 相似文献
60.