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1.
A series of cellular-automata (CA) models have been created, simulating relationships between water (or aqueous solutions) and solid surfaces of differing hydropathic (i.e., hydrophilic or hydrophobic) nature. Both equilibrium- and dynamic-flow models were examined, employing simple breaking and joining rules to simulate the hydropathic interactions. The CA simulations show that water accumulates near hydrophilic surfaces and avoids hydrophobic surfaces, forming concave-up and concave-down meniscuses, resp., under equilibrium conditions. In the dynamic-flow simulations, the flow rate of water was found to increase past a wall surface as the surface became less hydrophilic, reaching a maximum rate when the solid surface was of intermediate hydropathic state, and then declining with further increase in the hydrophobicity of the surface. Solution simulations show that non-polar solutes tend to achieve higher concentrations near hydrophobic-wall surfaces, whereas other hydrophobic/hydrophilic combinations of solutes and surfaces do not show such accumulations. Physical interpretations of the results are presented, as are some possible biological consequences. 相似文献
2.
Rodriguez J Spearman M Tharmalingam T Sunley K Lodewyks C Huzel N Butler M 《Journal of biotechnology》2010,150(4):509-518
Recombinant human interferon-beta (β-IFN), used in the therapeutic treatment of multiple sclerosis (MS), can be produced on a large-scale from genetically engineered Chinese hamster ovary (CHO) cells. However, its hydrophobicity causes non-reversible, molecular aggregation in culture. The parameters affecting aggregation were determined to be concentration, culture residence time, temperature and glycosylation. Although the protein can be produced in Escherichia coli in a non-glycosylated form, the addition of glycans confers a reduced rate of aggregation as well as a 10-fold higher bioactivity. We report on the application of a low temperature perfusion culture designed to control the parameters that cause aggregation. In this three-phase culture system there is a transition to a low temperature (32°C) in a batch mode prior to implementing perfusion at 1 volume/day using an acoustic cell separator. Perfusion at the low temperature resulted in a 3.5-fold increase in specific productivity and a 7-fold increase in volumetric productivity compared to the batch culture at 37°C. The percentage aggregation of β-IFN was reduced from a maximum of 43% in batch culture to a minimum of 5% toward the end of the perfusion phase. The glycosylation profile of all samples showed predominantly sialylated biantennary fucosylated structures. The extent of sialylation, which is important for bioactivity, was enhanced significantly in the perfusion culture, compared to the batch culture. 相似文献
3.
Vitaly V. Vostrikov Anna E. Daily Denise V. Greathouse Roger E. Koeppe II 《The Journal of biological chemistry》2010,285(41):31723-31730
The membrane-spanning segments of integral membrane proteins often are flanked by aromatic or charged amino acid residues, which may “anchor” the transmembrane orientation. Single spanning transmembrane peptides such as those of the WALP family, acetyl-GWW(LA)nLWWA-amide, furthermore adopt a moderate average tilt within lipid bilayer membranes. To understand the anchor residue dependence of the tilt, we introduce Leu-Ala “spacers” between paired anchors and in some cases replace the outer tryptophans. The resulting peptides, acetyl-GX2ALW(LA)6LWLAX22A-amide, have Trp, Lys, Arg, or Gly in the two X positions. The apparent average orientations of the core helical sequences were determined in oriented phosphatidylcholine bilayer membranes of varying thickness using solid-state 2H NMR spectroscopy. When X is Lys, Arg, or Gly, the direction of the tilt is essentially constant in different lipids and presumably is dictated by the tryptophans (Trp5 and Trp19) that flank the inner helical core. The Leu-Ala spacers are no longer helical. The magnitude of the apparent helix tilt furthermore scales nicely with the bilayer thickness except when X is Trp. When X is Trp, the direction of tilt is less well defined in each phosphatidylcholine bilayer and varies up to 70° among 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, and 1,2-dilauroyl-sn-glycero-3-phosphocholine bilayer membranes. Indeed, the X = Trp case parallels earlier observations in which WALP family peptides having multiple Trp anchors show little dependence of the apparent tilt magnitude on bilayer thickness. The results shed new light on the interactions of arginine, lysine, tryptophan, and even glycine at lipid bilayer membrane interfaces. 相似文献
4.
Schewkunow V Sharma KP Diez G Klemm AH Sharma PC Goldmann WH 《Biochemical and biophysical research communications》2008,366(2):500-505
A unique feature of protein networks in living cells is that they can generate their own force. Proteins such as non-muscle myosin II are an integral part of the cytoskeleton and have the capacity to convert the energy of ATP hydrolysis into directional movement. Non-muscle myosin II can move actin filaments against each other, and depending on the orientation of the filaments and the way in which they are linked together, it can produce contraction, bending, extension, and stiffening. Our measurements with differential scanning calorimetry showed that non-muscle myosin II inserts into negatively charged phospholipid membranes. Using lipid vesicles made of DMPG/DMPC at a molar ratio of 1:1 at 10 mg/ml in the presence of different non-muscle myosin II concentrations showed a variation of the main phase transition of the lipid vesicle at around 23 °C. With increasing concentrations of non-muscle myosin II the thermotropic properties of the lipid vesicle changed, which is indicative of protein-lipid interaction/insertion. We hypothesize that myosin tail binds to acidic phospholipids through an electrostatic interaction using the basic side groups of positive residues; the flexible, amphipathic helix then may partially penetrate into the bilayer to form an anchor. Using the stopped-flow method, we determined the binding affinity of non-muscle myosin II when anchored to lipid vesicles with actin, which was similar to a pure actin-non-muscle myosin II system. Insertion of myosin tail into the hydrophobic region of lipid membranes, a model known as the lever arm mechanism, might explain how its interaction with actin generates cellular movement. 相似文献
5.
秦岭地区玉竹根茎的脂溶性成分及其抑菌活性研究 总被引:3,自引:0,他引:3
从秦岭产玉竹(Polygonatum odoratum)根茎的石油醚萃取物中分离得到8个化合物,其中有5个化合物为首次从黄精属植物中得到,其结构分别为:(1)(24R/S)-9,19-环阿尔廷-25-烯-3β,24-二醇;(2)α-棕榈酸甘油酯;(3)棕榈酸甲酯;(4)二十八碳酸;(5)(Z)-6-十九碳烯酸。首次对化合物1的抗菌活性进行了测定,发现化合物1在浓度为10μg/mL时,对黄瓜炭疽病原菌的抑制率达到100%;在浓度为100μg/mL时,对灵杆菌的抑菌能力与红霉素相当。 相似文献
6.
环境中疏水性有机污染物(Hydrophobic organic pollutants,HOPs)的浓度日益增加,获取HOPs高效降解功能微生物能有效提高HOPs污染治理效率。近年来,利用两相系统促进HOPs微生物降解转化的研究已取得一定进展。本文重点从两相系统的结构特点及其富集HOPs降解功能微生物的原理、主要影响因素和应用情况等方面进行综述,并在此基础上对两相系统在毒害性HOPs微生物加速降解脱毒中所存在的主要问题及其应用前景进行讨论和展望。 相似文献
7.
Mrigendra B. Karmacharya Yoon-Jin Lee Jae-Won Soh 《Archives of biochemistry and biophysics》2010,493(2):242-248
Protein kinase C delta (PKCδ) is one of the important isoforms of PKCs that regulate various cellular processes, including cell survival and apoptosis. Studies have shown that activation of PKCδ is correlated with apoptosis in various cell types, depending upon various stimuli. Phosphorylation of Thr505, Ser643 and Ser662 is crucial in activation of PKCδ. Furthermore, phosphorylation of tyrosine residues, in particular that of Tyr311, is associated with PKCδ activation and induction of apoptosis. Here, we generated a hydrophobic motif phosphorylation-deficient mutant of PKCδ (PKCδ-S662A) by mutating Ser662 to Ala, and studied the effect of this mutation in inducing apoptosis in L929 murine fibroblasts. We report that this mutation renders PKCδ apoptotically more active. Furthermore, we found that the mutant PKCδ-S662A is tyrosine-phosphorylated and translocated to the membrane faster than its wild-type counterpart. 相似文献
8.
平菇萃取液经酸性沉淀、热变性、Phenyl-Sepharose CL-4B疏水亲和层析和DEAE-Cellulose 52离子交換层析分冉出了电泳纯的真菌钙调素。在比较钙调素对磷酸二酯酶活化的能力和ELISA实验的免疫亲和力对发现,平菇钙调素与猪脑钙调素的生物活性有较大差异,提示在钙调素定量测定中有必要考虑到标准钙调素与样品钙调素之间的同源性差异。 相似文献
9.
《Bioorganic & medicinal chemistry》2020,28(21):115720
An organic small-molecular drug, 4-(1H-indol-3-yl)-2-(p-tolyl)quinazoline-3-oxide 1a was synthesized. It was employed to investigate the binding interaction and mechanism with human serum albumin (HSA). The experimental results indicated that the fluorescence quenching of HSA by 1a is a static quenching process and formation 1a-HSA complex. The site competition experiments revealed that the combination of 1a on HSA are hydrophobic interactions in the IIA domain and hydrogen bonds in IIIA domain of HSA, and the hydrophobic interactions of 1a on HSA are stronger than that of hydrogen bonds. These results were also confirmed by molecular docking theoretic analysis and ANS-hydrophobic fluorescent probe experiment. Synchronous fluorescence experiments showed that the polarity of HSA microenvironment was increase in the interaction process of 1a with HSA. The results of binding distance explored indicated that the combination distance between 1a and HSA is 3.63 nm, which is between 0.5R0 and 1.5R0, revealing the energy transfer between HSA and 1a is non-radiative. These results are very helpful for people to screen out high efficient indoloquinazoline drugs. 相似文献
10.
TAR DNA binding protein 43 (TDP-43) is a key target in amyotrophic lateral sclerosis (ALS) treatment. Here, based on hydrophobic tagging strategy, we designed and synthesized a series of single or double hydrophobic tags conjugated peptides D1-D8. Among them, it was found that D4 displayed strongest ability to induce TDP-43 degradation in cells. D4 could reduce TDP-43 induced cytotoxicity. Besides, D4 could reduce TDP-43 levels in a transgenic drosophila model. 相似文献