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排序方式: 共有309条查询结果,搜索用时 31 毫秒
221.
Kuhn P Lesley SA Mathews II Canaves JM Brinen LS Dai X Deacon AM Elsliger MA Eshaghi S Floyd R Godzik A Grittini C Grzechnik SK Guda C Hodgson KO Jaroszewski L Karlak C Klock HE Koesema E Kovarik JM Kreusch AT McMullan D McPhillips TM Miller MA Miller M Morse A Moy K Ouyang J Robb A Rodrigues K Selby TL Spraggon G Stevens RC Taylor SS van den Bedem H Velasquez J Vincent J Wang X West B Wolf G Wooley J Wilson IA 《Proteins》2002,49(1):142-145
222.
Thomas Scior Günter Raddatz Rocio Figueroa Hermann J. Roth Hans A. Bisswanger 《Journal of molecular modeling》1997,3(8):332-337
Despite the very close structural relationship between dapsone (4,4′-diaminodiphenyl sulfone, 4,4′ sulphonyldianiline, diaphenyl sulphone, DDS) and sulfanilamide (p-aminobenzene sulfonamide), being the prototype of all other sulfonamides, only dapsone shows remarkable efficient pharmacological activity against Mycobacterium leprae. Cells of certain micro-organism need para-aminobenzoic acid (PABA), the latter playing the role of natural substrate to biosynthesis of folic acid. Sufones and sulfonamides show competitive antagonism as chemical analogs of PABA. It is most surprising that, despite of sharing this molecular mechanism, only dapsone shows anti-leprosy activity in vivo. The study was accomplished using molecular mechanics (SYBYL) and semiempirical methods (MOPAC). The calculations of aromaticity, charges, protonation by MOPAC, and of lipophilicity by our empirical program LIPOP(hilicity) give evidence that dapsone is more lipophilic (log P values 0.97) than sulfanilamide (-0.67). The extremely lipophilic cell wall of Mycobacterium leprae contributes to the surprising difference in anti-leprosy activity. Sulfonamides are more or less deprotonated (45 to 99 %) at physiological pH units, whereas dapsone is totally undissociated. This results in different permeability rates into the bacterial cells in vivo. Compared to other sulfones and sulfonamides, the unique combination of high lipophilicity and low ionic dissociation favors anti-leprotic potency in dapsone. On principle, amide groups do not hinder activity, but cause acidity and subsequently dissociation. 相似文献
223.
On the basis of the homodimeric X-ray structure of dihydrolipoamide dehydrogenase from Azotobacter vinelandii we demonstrate by protein modeling techniques that two dimeric units of this enzyme can associate to a tetrameric structure with intense contacts between the building blocks. Complementary structures of the respective other unit in the tetramer contribute to the active sites. The coenzyme FAD becomes shielded from the environment, thus its binding is stabilized. By energy minimization techniques binding energies and RMS-values were computed and the contact areas between the building blocks were determined to quantify the interaction. In the cell tetramerization of dihydrolipoamide dehydrogenase will be realized upon its incorporation as an enzyme component into the pyruvate dehydrogenase multienzyme complex and will have consequences for the structure and subunit stoichiometry of the complex. Especially, the multiplicity of the three enzyme components, i.e. pyruvate dehydrogenase, dihydrolipoamide acetyltransferase and dihydrolipoamide dehydrogenase in the enzyme complex must be 24:24:24 instead of 24:24:12 assumed so far.Electronic Supplementary Material available. 相似文献
224.
Bodian and Nissl procedures were combined to stain dissociated mouse spinal cord cells cultured on coverslips. The Bodian technique stains fine neuronal processes in great detail as well as an intracellular fibrillar network concentrated around the nucleus and in proximal neurites. The Nissl stain clearly delimits neuronal cytoplasm in somata and in large dendrites. A combination of these techniques allows the simultaneous depiction of neuronal perikarya and all afferent and efferent processes. Costaining with little background staining by either procedure suggests high specificity for neurons. This procedure could be exploited for routine network analysis of cultured neurons. 相似文献
225.
226.
Single-cell suspensions of splenic lymphocytes from 5- to 6-month-old C57BL/6 mice were cryopreserved using cooling rates ranging from ?0.25 to ?10.0 °C/min with the microprocessor-controlled cooling system developed in our laboratory. The cells (30 × 106 cells/ml) were suspended in RPMI 1640 containing 10% FCS and 10% DMSO, and a total volume of 1.75 ml was frozen. Fluorescein-diacetate staining identified viable cells in unfrozen controls and frozen-thawed suspensions. Functional capacity was assessed in vitro by the incorporation of [3H]thymidine by dividing cells activated with graded concentrations of the T-lymphocyte mitogens, PHA-P and Con A, and the B-lymphocyte mitogen, LPS. High percentages of viable cells were recovered after cooling at rates ranging from ?0.5 to ?5.0 °C/min, as compared with those of unfrozen control suspensions. Incorporation of [3H]thymidine by T and B cells reached similar levels after cooling at rates ranging from ?0.25 to ?5.0 °C/min, and the percentage incorporation of [3H]thymidine as compared with that of unfrozen cells was 80–100%, except for T lymphocytes activated with PHA-P after cooling at ?5.0 °C/min. The relative response of cell suspensions to T- and B-cell mitogens, the relative mitogenic index, was unchanged from that of unfrozen controls in suspensions cooled at all rates including two (?0.25 and ?10.0 °C/min), which permitted recovery of only 55% of unfrozen cells. The importance of the constant cooling rates and rapid compensation for heat released at the phase change using the microprocessor-controlled system and of precise determinations of cellular viability and function are discussed and related to the apparent protection conferred on subpopulations of murine lymphocytes using cooling rates ranging from ? 0.25 to ?10.0 °C/min. 相似文献
227.
Guenter Weigel Andrea Griesmacher Cyril Toma Christian Leukauf Wolfgang Schreiner Ernst Wolner 《Free radical biology & medicine》1994,17(6):577-585
Human umbilical vein endothelial cells were incubated with Bretschneider and St. Thomas II cardioplegic solution followed by a stimulation with cumene hydroperoxide (CHPO), which was used as an oxygen radicals generating agent. A statistically significant decrease of intracellular high energy phosphates (adenosine-5-triphosphate: ATP; creatine phosphate; CP) compared to controls was observed in response to Bretschneider cardioplegia and CHPO. Furthermore, significant rises in prostaglandin I2 (prostacyclin; PGI2) production and lipidperoxidation were measured. The authors failed to record such alterations of endothelial cell metabolism for the St. Thomas II cardioplegic solution. They could also demonstrate that the cellular protection against oxygen radicals exerted by the St. Thomas II solution is attributable to procaine. The enhanced cytotoxicity of CHPO observed in presence of the Bretschneider solution was found to be partially caused by its constituent
-histidine, which led to significant decreases of high energy phosphates and increased lipidperoxidation when cells were subsequently treated with CHPO. However, alterations of high energy phosphate content initiated by CHPO and amplified by the Bretschneider solution could not be inhibited by adding procaine. Simultaneous pretreatment of cells with the Bretschneider solution and procaine and stimulation with CHPO resulted in decreases of ATP and CP, as observed using the Bretschneider cardioplegia alone. 相似文献
228.
Ververidis F Trantas E Douglas C Vollmer G Kretzschmar G Panopoulos N 《Biotechnology journal》2007,2(10):1235-1249
Plant natural products derived from phenylalanine and the phenylpropanoid pathways are impressive in their chemical diversity and are the result of plant evolution, which has selected for the acquisition of large repertoires of pigments, structural and defensive compounds, all derived from a phenylpropanoid backbone via the plant-specific phenylpropanoid pathway. These compounds are important in plant growth, development and responses to environmental stresses and thus can have large impacts on agricultural productivity. While plant-based medicines containing phenylpropanoid-derived active components have long been used by humans, the benefits of specific flavonoids and other phenylpropanoid-derived compounds to human health and their potential for long-term health benefits have only been recognized more recently. In this part of the review, we discuss in detail the recent strategies and achievements used in the reconstruction of multienzyme pathways in plants and microbes in an effort to be able to attain higher amounts of the desired flavonoids and stilbenoids exploiting their beneficial properties as analyzed extensively in Part I of this review. 相似文献
229.
230.