全文获取类型
收费全文 | 2007篇 |
免费 | 115篇 |
国内免费 | 4篇 |
专业分类
2126篇 |
出版年
2024年 | 7篇 |
2023年 | 16篇 |
2022年 | 65篇 |
2021年 | 89篇 |
2020年 | 45篇 |
2019年 | 52篇 |
2018年 | 68篇 |
2017年 | 59篇 |
2016年 | 84篇 |
2015年 | 118篇 |
2014年 | 129篇 |
2013年 | 155篇 |
2012年 | 188篇 |
2011年 | 186篇 |
2010年 | 86篇 |
2009年 | 75篇 |
2008年 | 110篇 |
2007年 | 72篇 |
2006年 | 78篇 |
2005年 | 69篇 |
2004年 | 53篇 |
2003年 | 52篇 |
2002年 | 33篇 |
2001年 | 21篇 |
2000年 | 19篇 |
1999年 | 15篇 |
1998年 | 10篇 |
1997年 | 10篇 |
1996年 | 8篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 9篇 |
1992年 | 13篇 |
1991年 | 8篇 |
1990年 | 11篇 |
1989年 | 7篇 |
1987年 | 4篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1978年 | 4篇 |
1977年 | 7篇 |
1975年 | 4篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1967年 | 4篇 |
排序方式: 共有2126条查询结果,搜索用时 0 毫秒
991.
Yang RY Kizer D Wu H Volckova E Miao XS Ali SM Tandon M Savage RE Chan TC Ashwell MA 《Bioorganic & medicinal chemistry》2008,16(10):5635-5643
ARQ 501 (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b] pyran-5,6-dione), a synthetic version of beta-Lapachone, is a promising anti-cancer agent currently in multiple Phase II clinical trials. Promising anti-cancer activity was observed in Phase I and Phase II trials. Metabolism by red blood cells of drugs is an understudied area of research and the metabolites arising from oxidative ring opening (M2 and M3), decarbonylation/ring contraction (M5), and decarbonylation/oxidation (M4 and M6) of ARQ 501 offer a unique opportunity to provide insight into these metabolic processes. Since these metabolites were not detected in in vitro incubations of ARQ 501 with liver microsomes and were structurally diverse, confirmation by chemical synthesis was considered essential. In this report, we disclose the synthetic routes employed and the characterization of the reference standards for these blood metabolites as well as additional postulated structures, which were not confirmed as metabolites. 相似文献
992.
Rapid mechanisms of glucocorticoid signaling in the Leydig cell 总被引:1,自引:0,他引:1
Stress-mediated elevations in circulating glucocorticoid levels lead to corresponding rapid declines in testosterone production by Leydig cells in the testis. In previous studies we have established that glucocorticoids act on Leydig cells directly, through the classic glucocorticoid receptor (GR), and that access to the GR is controlled prior to the GR by a metabolizing pathway mediated by the type 1 isoform of 11beta-hydroxysteroid dehydrogenase (11betaHSD1). This enzyme is bidirectional (with both oxidase and reductase activities) and in the rat testis is exclusively localized in Leydig cells where it is abundantly expressed and may catalyze the oxidative inactivation of glucocorticoids. The predominant reductase direction of 11betaHSD1 activity in liver cells is determined by an enzyme, hexose-6-phosphate dehydrogenase (H6PDH), on the luminal side of the smooth endoplasmic reticulum (SER). Generation of the pyridine nucleotide cofactor NADPH by H6PDH stimulates the reductase direction of 11betaHSD1 resulting in increased levels of active glucocorticoids in liver cells. Unlike liver cells, steroidogenic enzymes including 17beta-hydroxysteroid dehydrogenase 3 (17betaHSD3) forms the coupling with 11betaHSD1. Thus the physiological concentrations of androstenedione serve as a substrate for 17betaHSD3 utilizing NADPH to generate NADP+, which drives 11betaHSD1 in Leydig cells primarily as an oxidase; thus eliminating the adverse effects of glucocorticoids on testosterone production. At the same time 11betaHSD1 generates NADPH which promotes testosterone biosynthesis by stimulating 17betaHSD3 in a cooperative cycle. This enzymatic coupling constitutes a rapid mechanism for modulating glucocorticoid control of testosterone biosynthesis. Under stress conditions, glucocorticoids also have rapid actions to suppress cAMP formation thus to lower testosterone production. 相似文献
993.
Protein kinase C activation promotes microtubule advance in neuronal growth cones by increasing average microtubule growth lifetimes 总被引:4,自引:0,他引:4
Kabir N Schaefer AW Nakhost A Sossin WS Forscher P 《The Journal of cell biology》2001,152(5):1033-1044
We describe a novel mechanism for protein kinase C regulation of axonal microtubule invasion of growth cones. Activation of PKC by phorbol esters resulted in a rapid, robust advance of distal microtubules (MTs) into the F-actin rich peripheral domain of growth cones, where they are normally excluded. In contrast, inhibition of PKC activity by bisindolylmaleimide and related compounds had no perceptible effect on growth cone motility, but completely blocked phorbol ester effects. Significantly, MT advance occurred despite continued retrograde F-actin flow-a process that normally inhibits MT advance. Polymer assembly was necessary for PKC-mediated MT advance since it was highly sensitive to a range of antagonists at concentrations that specifically interfere with microtubule dynamics. Biochemical evidence is presented that PKC activation promotes formation of a highly dynamic MT pool. Direct assessment of microtubule dynamics and translocation using the fluorescent speckle microscopy microtubule marking technique indicates PKC activation results in a nearly twofold increase in the typical lifetime of a MT growth episode, accompanied by a 1.7-fold increase and twofold decrease in rescue and catastrophe frequencies, respectively. No significant effects on instantaneous microtubule growth, shortening, or sliding rates (in either anterograde or retrograde directions) were observed. MTs also spent a greater percentage of time undergoing retrograde transport after PKC activation, despite overall MT advance. These results suggest that regulation of MT assembly by PKC may be an important factor in determining neurite outgrowth and regrowth rates and may play a role in other cellular processes dependent on directed MT advance. 相似文献
994.
Viable airborne fungi in Riyadh, Saudi Arabia 总被引:7,自引:4,他引:3
Abdulrahman Sulaiman Al-Suwaine Syed Mohammed Hasnain Ali Hassan Bahkali 《Aerobiologia》1999,15(2):121-130
An aerobiological study to identify and quantify allergenic fungi and their seasonal fluctuations was conducted at two different sites, (Al-Batha, a more developed area in the south and Al-Ulia, a less developed area in the north) in Riyadh city, using portable Personal Volumetric Air Sampler (Burkard Manufacturing Co., England). Sampling was conducted twice a week in both the morning and in the afternoon at both sites, for a period of 12 months. Airborne fungi were grouped into major and minor components depending upon their frequency of appearance and catch percentage in the air. Cladosporium spp., Penicillium spp., Aspergillus spp., Alternaria spp. and Ulocladium spp. were included as major components. Minor components included Drechslera spp., Rhizopus spp., Fusarium spp. and Stachybotryis spp. In general, higher concentrations of fungi were found at the developed (Al-Batha) site than at the less developed (Al-Ulia) site, both in the morning and in the afternoon. 相似文献
995.
A method for the separation of one cell type present in small number from a predominant mixture of cell types using macroscopic polystyrene beads is demonstrated. An antibody specific to murine leukocytes (CD45) was adsorbed to the surface of the beads. Beads and murine hybridoma B cells were placed in test tubes and periodically inverted at fixed time intervals, causing the beads to settle through the suspension under creeping flow conditions. Capture was dependent upon interception: the captured cells must have traveled along streamlines that brought them to within a cell radius of the bead surface. B cells attached to 99-micrometer beads (maximum shear rate 8.1 s-1) were captured with greater efficiency but in lesser quantity than those attached to 170-micrometer beads (maximum shear rate 13.9 s-1). Cell capture unexpectedly reached a plateau in less than 2 h, a phenomenon that appears to involve changes in both the cells and the beads. Capture of cells was effective out to dilutions of 1:10 000 with purity in the captured population of better than 74%. This method allows for the study of physical parameters important for cell attachment and capture as well as for practical separation of rare cells. 相似文献
996.
997.
Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones 总被引:13,自引:0,他引:13
We have used multimode fluorescent speckle microscopy (FSM) and correlative differential interference contrast imaging to investigate the actin-microtubule (MT) interactions and polymer dynamics known to play a fundamental role in growth cone guidance. We report that MTs explore the peripheral domain (P-domain), exhibiting classical properties of dynamic instability. MT extension occurs preferentially along filopodia, which function as MT polymerization guides. Filopodial bundles undergo retrograde flow and also transport MTs. Thus, distal MT position is determined by the rate of plus-end MT assembly minus the rate of retrograde F-actin flow. Short MT displacements independent of flow are sometimes observed. MTs loop, buckle, and break as they are transported into the T-zone by retrograde flow. MT breakage results in exposure of new plus ends which can regrow, and minus ends which rapidly undergo catastrophes, resulting in efficient MT turnover. We also report a previously undetected presence of F-actin arc structures, which exhibit persistent retrograde movement across the T-zone into the central domain (C-domain) at approximately 1/4 the rate of P-domain flow. Actin arcs interact with MTs and transport them into the C-domain. Interestingly, although the MTs associated with arcs are less dynamic than P-domain MTs, they elongate efficiently as a result of markedly lower catastrophe frequencies. 相似文献
998.
Chowdhury EK Akaishi Y Nagata S Misono H 《Bioscience, biotechnology, and biochemistry》2003,67(2):438-441
The structural gene for NAD+-dependent 3-hydroxyisobutyrate dehydrogenase (EC 1.1.1.31) from Pseudomonas putida E23 was cloned in Escherichia coli cells to obtain a large amount of the enzyme and its nucleotides were sequenced to study its structural relationship with other proteins. The gene encoded a polypeptide containing 295 amino acid residues and was in a cluster with the gene for methylmalonate semialdehyde dehydrogenase. Transformed E. coli cells overproduced 3-hydroxyisobutyrate dehydrogenase, and the recombinant enzyme was purified to homogeneity with a high yield. Lysine and asparagine residues, which are important in catalysis of the 3-hydroxyacid dehydrogenase family, are conserved in this enzyme. 相似文献
999.
Experimental infection of twenty species of Indian marine crabs with white spot syndrome virus (WSSV) 总被引:11,自引:0,他引:11
Hameed AS Balasubramanian G Musthaq SS Yoganandhan K 《Diseases of aquatic organisms》2003,57(1-2):157-161
Twenty species of Indian marine crabs were experimentally infected with white spot syndrome virus (WSSV), via the oral route and intramuscular injection, to determine their viral susceptibility. We determined that 16 species (Calappa philargius, Charybdis annulata, C. lucifera, Doclea hybrida, Grapsus albolineatus, Halimede ochtodes, Liagore rubronaculata, Lithodes maja, Matuta miersi, Paradorippe granulata, Parthenope prensor, Philyra syndactyla, Podophthalmus vigil, Portunus sanquinolentus, Scylla serrata and Thalamita danae) were susceptible and 4 (Atergatis integerrimus, Charybdis natator, Demania splendida or Menippe rumphii) were refractive at 50 d post-infection (p.i.). The presence of WSSV in these crabs was confirmed by PCR tests, histology and bioassay. WSSV was found in the gill, heart, eyestalks, striated muscle and cephalothoraxic tissue. The 4 WSSV-refractive species represent potential reservoirs or carriers of WSSV. 相似文献
1000.
Capsaicin is the pungent ingredient present in hot peppers of the genus Capsicum. Capsaicin's effect on sensory neurons has been well studied; however, its effect on non-neuronal cells is still not fully understood. This study was undertaken to evaluate the effect of capsaicin on erythrocyte membrane enzymes: Na+/K(+)-ATPase and Ca(2+)-ATPase. Treatment with capsaicin (0.01-100 microM) caused a transient increase in the activities of both enzymes; the effect declined at lower concentrations of capsaicin, and no significant effect was observed at 0.01 microM capsaicin. The effect of capsaicin was fast with a significant (p<0.01) activation of enzyme activity observed within minutes of incubation. The findings on the effect of capsaicin on human erythrocyte membrane enzymes Na+/K(+)-ATPase and Ca(2+)-ATPase signify the importance of the non-neuronal effects of capsaicin, and the need for evaluating the physiological impact of high capsaicin (capsicum) consumption in some regions of the world. 相似文献