全文获取类型
收费全文 | 3279篇 |
免费 | 243篇 |
出版年
2023年 | 20篇 |
2022年 | 16篇 |
2021年 | 80篇 |
2020年 | 51篇 |
2019年 | 69篇 |
2018年 | 83篇 |
2017年 | 64篇 |
2016年 | 111篇 |
2015年 | 162篇 |
2014年 | 190篇 |
2013年 | 192篇 |
2012年 | 250篇 |
2011年 | 206篇 |
2010年 | 152篇 |
2009年 | 116篇 |
2008年 | 158篇 |
2007年 | 163篇 |
2006年 | 133篇 |
2005年 | 132篇 |
2004年 | 124篇 |
2003年 | 126篇 |
2002年 | 124篇 |
2001年 | 43篇 |
2000年 | 29篇 |
1999年 | 20篇 |
1998年 | 45篇 |
1997年 | 19篇 |
1996年 | 23篇 |
1995年 | 28篇 |
1994年 | 21篇 |
1993年 | 17篇 |
1992年 | 30篇 |
1991年 | 24篇 |
1990年 | 19篇 |
1989年 | 24篇 |
1988年 | 22篇 |
1987年 | 16篇 |
1986年 | 12篇 |
1985年 | 17篇 |
1984年 | 22篇 |
1983年 | 10篇 |
1982年 | 14篇 |
1981年 | 19篇 |
1980年 | 15篇 |
1979年 | 11篇 |
1978年 | 14篇 |
1976年 | 14篇 |
1973年 | 16篇 |
1971年 | 12篇 |
1966年 | 9篇 |
排序方式: 共有3522条查询结果,搜索用时 234 毫秒
981.
Eico Kimura Claudi K. Frigeri Hugo A. Armelin 《Molecular and cellular biochemistry》1993,124(1):23-32
We previously reported that ACTH, but not dibutyryl cAMP, rapidly induces the c-fos proto-oncogene in Y-1 adrenocortical cells.Here we show that PMA induces c-fos with similar kinetics when compared with ACTH (0.5–1 h peak) but reaches only 60% of the maximal ACTH induction and dcAMP is a weak c-fos inducer (15% of ACTH). However, combination of PMA and dcAMP has a synergistic effect leading to maximal c-fos induction. c-fos expression may play a role in the RNA synthesis-dependent corticosteroidogenesis response and/or growth regulation by ACTH.We also show that, in contrast to dcAMP, PMA is a poor steroidogenesis stimulator (15 to 17% of maximum ACTH-stimulated level), its activity being completely dependent on RNA synthesis. Combination of dcAMP and PMA yields an additive steroidogenesis stimulation, an effect that is also dependent on RNA synthesis. Although no strict correlation was found between c-fos induction and early steroidogenesis stimulation, particularly with respect to cAMP derivatives, the results suggest that a PKC pathway is likely to cooperate with the classical cAMP-PKA pathway in adrenal cells' RNA-dependent steroidogenesis.Abbreviations ACTH
Adrenocorticotropic Hormone
- PMA
Phorbol-12-Myrystate-13-Acetate
- dcAMP
dibutyryl cyclic AMP
- DME
Dulbecco's Modified Eagle's minimal medium
- FCS
Fetal Calf Serum 相似文献
982.
Hugo Schweke Qifang Xu Gerardo Tauriello Lorenzo Pantolini Torsten Schwede Frédéric Cazals Alix Lhéritier Juan Fernandez-Recio Luis Angel Rodríguez-Lumbreras Ora Schueler-Furman Julia K. Varga Brian Jiménez-García Manon F. Réau Alexandre M. J. J. Bonvin Castrense Savojardo Pier-Luigi Martelli Rita Casadio Jérôme Tubiana Haim J. Wolfson Romina Oliva Didier Barradas-Bautista Tiziana Ricciardelli Luigi Cavallo Česlovas Venclovas Kliment Olechnovič Raphael Guerois Jessica Andreani Juliette Martin Xiao Wang Genki Terashi Daipayan Sarkar Charles Christoffer Tunde Aderinwale Jacob Verburgt Daisuke Kihara Anthony Marchand Bruno E. Correia Rui Duan Liming Qiu Xianjin Xu Shuang Zhang Xiaoqin Zou Sucharita Dey Roland L. Dunbrack Emmanuel D. Levy Shoshana J. Wodak 《Proteomics》2023,23(17):2200323
Reliably scoring and ranking candidate models of protein complexes and assigning their oligomeric state from the structure of the crystal lattice represent outstanding challenges. A community-wide effort was launched to tackle these challenges. The latest resources on protein complexes and interfaces were exploited to derive a benchmark dataset consisting of 1677 homodimer protein crystal structures, including a balanced mix of physiological and non-physiological complexes. The non-physiological complexes in the benchmark were selected to bury a similar or larger interface area than their physiological counterparts, making it more difficult for scoring functions to differentiate between them. Next, 252 functions for scoring protein-protein interfaces previously developed by 13 groups were collected and evaluated for their ability to discriminate between physiological and non-physiological complexes. A simple consensus score generated using the best performing score of each of the 13 groups, and a cross-validated Random Forest (RF) classifier were created. Both approaches showed excellent performance, with an area under the Receiver Operating Characteristic (ROC) curve of 0.93 and 0.94, respectively, outperforming individual scores developed by different groups. Additionally, AlphaFold2 engines recalled the physiological dimers with significantly higher accuracy than the non-physiological set, lending support to the reliability of our benchmark dataset annotations. Optimizing the combined power of interface scoring functions and evaluating it on challenging benchmark datasets appears to be a promising strategy. 相似文献
983.
Novel Subtype of Peroxisomal Acyl-CoA Oxidase Deficiency and Bifunctional Enzyme Deficiency with Detectable Enzyme Protein: Identification by Means of Complementation Analysis 总被引:4,自引:1,他引:3 下载免费PDF全文
Yasuyuki Suzuki Nobuyuki Shimozawa Shigehiro Yajima Shunji Tomatsu Naomi Kondo Yukikatsu Nakada Shinjiro Akaboshi Mizue Iai Yuzo Tanabe Takashi Hashimoto Ronald J. A. Wanders Ruud B. H. Schutgens Hugo W. Moser Tadao Orii 《American journal of human genetics》1994,54(1):36-43
We describe four infants with a novel subtype of an isolated deficiency of one of the peroxisomal β-oxidation enzymes with detectable enzyme protein. The patients showed characteristic clinical and biochemical abnormalities, including hypotonia, psychomotor retardation, hepatomegaly, typical facial appearance, accumulation of very-long-chain fatty acids, and decreased lignoceric acid oxidation. However, β-oxidation enzyme proteins were detected by immunoblot analyses, and large peroxisomes were identified by immunofluorescence staining. In order to identify the underlying defect in these patients, complementation analysis was introduced using fibroblasts from these patients and patients with an established deficiency of either acyl-CoA oxidase or bifunctional enzyme, as identified by immunoblotting. In the complementing combinations, fused cells showed increased lignoceric acid oxidation, resistance against 1-pyrene dodecanoic acid/UV selection, and normalization of the size and the distribution of peroxisomes. The results indicate that two patients with a more severe clinical course were suffering from bifunctional enzyme deficiency and that the other two infants, who were siblings and had a less severe clinical presentation, were the first patients with acyl-CoA oxidase deficiency with detectable enzyme protein. 相似文献
984.
Ignace Hanssens Willy Herreman Jean-Claude van Ceunebroeck Hugo Dangreau Constant Gielens Gisele Preaux Frans van Cauwelaert 《生物化学与生物物理学报:生物膜》1983,728(3):293-304
We investigated the interaction between α-lactalbumin and sonicated dimyristoylphosphatidylcholine at pH 4 and different temperatures. (1) At 23°C and lipid-to-protein molar ratios below 170, the interaction results in a disruption of the original vesicles to form smaller complex particles. By the sedimentation velocity method we determined for this particle a molar mass of (1.05 ± 0.16) · 106 g·mol?1. The lipid-to-protein molar ratio within the complex particle is 70/1, as earlier estimated. It follows that there are approximately 1200 lipid and 17 α-lactalbumin molecules per particle. At molar ratios above 170, α-lactalbumin strongly associates with the vesicles. In this case the vesicle entity remains. The ability of α-lactalbumin to break up the vesicles at this temperature is determined by the number of protein molecules which are required in the complex particle. (2) By means of fluorescence polarization of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene and energy transfer of the tryptophan groups of the protein to 1,3-(1,1′-dipyrenyl)propane located in the hydrocarbon region of the vesicles, it is shown that with increasing temperature above 25°C, complexes of decreasing internal lipid-to-protein molar ratio are formed. However, by electron microscopy we show that the overall size of these complexes remains approximately the same, i.e., bars with dimensions . A temperature-reversible transformation occurs between these complexes, which cannot be isolated by gel chromatography. In contrast, the complex of molar ratio 70/1 remains stable at lower temperatures. 相似文献
985.
CELLULAR DISTRIBUTION OF 16S ACETYLCHOLINESTERASE 总被引:12,自引:12,他引:0
Multiple molecular forms of acetylcholinesterase (AChE; EC 3.1.1.7), in crude extracts of various tissues from the rat, were distinguished by velocity sedimentation analysis on linear sucrose gradients. Skeletal muscle samples containing end-plate regions showed three different forms of AChE with apparent sedimentation coefficients of 16, 10 and 4s. The 16s form was not detected in non-innervated regions of skeletal muscle, large intestine smooth muscle, whole brain tissue, red blood cells or plasma. Spinal cord, a predominantly motor cranial nerve and mixed (sensory and motor) peripheral nerves contained 16, 10, 6.5 and 4S AChE. Ventral motor roots, supplying the sciatic nerve, contained these four forms of the enzyme, while corresponding dorsal sensory roots were devoid of the 16S form. The 16s-AChE confined to ventral roots can be attributed totally to motor neurons and not to Schwann cells composing these roots. Whether the 16s-AChE presently found in motor nerves has chemical identity with that found at motor end-plates is the basis of future experiments. 相似文献
986.
The construction of a highly sensitive microbore amino acid analyzer is described. It is based on a standard column chromatographic separation technique with fluorometric detection utilizing o-phthalaldehyde. This analyzer has several desirable features: low column chromatographic pressure, high sensitivity, and easy maintenance. Good precision at a level of 10 pmol is obtained and as little as 0.2 μg protein has been hydrolyzed for composition analysis. It incorporates the use of the single-column method and constant molarity buffers to shorten the analysis time. It is fully automatic and capable of analyzing 130 samples within 7 days with attention required only for reloading 20 samples while the instrument is in operation. Amino acid composition determination based on the peak area and the peak height is discussed. 相似文献
987.
Like phlorizin, two glycosidic esters of phlorizin, the 4-azido-2-nitrobenzoate (ANB-phlorizin) and the 2-nitrobenzoate (NB-phlorizin) were found to be effective inhibitors of SO42? equilibrium exchange at the outer but not at the inner membrane surface of the human erythrocyte ghost. After photolysis of ghost suspensions in the presence of extracellular ANB-phlorizin an irreversible inhibition of SO42? exchange was observed, while photolysis of intracellular ANB-phlorizin was without effect. After photolysis in the presence of extracellular or intracellular tritiated ANB-phlorizin gel electrophoresis of the labelled membranes revealed similar locations of binding. These findings suggest that the sidedness of action of ANB-phlorizin could not be related to inaccessibility of the inner membrane surface for the agent but that inhibition occurs via binding to fixed sites at the outer membrane surface that are not associated with a mobile carrier which crosses the membrane. 相似文献
988.
Hugo J. Gorissen Jean-Pierre Van Hoeck Anne M. Mockel Guido H. Journe Claude Delatour Valry R. Libert 《Chirality》1992,4(5):286-294
Both (R)- and (S)-4-hydroxypentylaminoacetamide have been synthesized by reductive amination of glycinamide on the γ-valerolactols corresponding to (R)- and (S)-γ-valerolactone, respectively. These enantiomeric lactones were readily obtained in high enantiomeric excess (ee) by enzymic porcine pancreatic lipase (PPL) kinetic resolution of rac-methyl γ-hydroxyvalerate. © 1992 Wiley-Liss, Inc. 相似文献
989.
Zenaide S. Ferreira Nidia C. Roque Otto R. Gottlieb Hugo E. Gottlieb 《Phytochemistry》1982,21(11):2756-2758
The trunk wood of Licaria chrysophylla contains rel-(7S, 8R, 1′S, 5′S)-Δ8′-3,3′,5′-trimethoxy-4,5-methylenedioxy-1′,4′,5′,6′- tetrahydro-4′-oxo-7.1′,8.0.2′-neolignan (chrysophyllin A), which differs from all other known benzofuranoid neolignans by showing 7.1′ (rather than 8.1′) and 8.0.2′ (rather than 7.0.2′) linkages between the propenylphenol and allylphenol derived moieties. 相似文献
990.
Ming Tien Lee A. Morehouse John R. Bucher Steven D. Aust 《Archives of biochemistry and biophysics》1982,218(2):450-458
Experiments were performed which illustrate the various ways EDTA can influence lipid peroxidation. Either detergent-dispersed linoleate, or liposomes made from extracted microsomal phospholipids were utilized as substrates for peroxidation. Peroxidation was accomplished using Fe2+ or Fe3+. In systems utilizing Fe2+, EDTA chelation facilitated Fe2+ autoxidation which in turn caused peroxidation of detergent-dispersed linoleate. Peroxidation was not initiated during EDTA-Fe2+ autoxidation when the substrate lipids were in a liposomal configuration. Systems utilizing Fe3+ required an enzyme (either xanthine oxidase or NADPH-cytochrome P450 reductase) to reduce the iron for peroxidative activity. EDTA chelation of Fe3+ enhanced the xanthine oxidase and NADPH-cytochrome P450 reductase-catalyzed peroxidation of detergent-dispersed linoleate, presumably by facilitating the reduction of Fe3+. Catalase and mannitol inhibited both EDTA-Fe2+- and EDTA-Fe3+-dependent lipid peroxidation. EDTA-Fe3+ was not capable of initiating peroxidation of phospholipid liposomes following enzymatic reduction by either enzyme, but ADP-chelated iron effectively initiated liposomal peroxidation in similar systems. With xanthine oxidase-catalyzed peroxidation of liposomes with ADP-Fe3+, the inclusion of EDTA-Fe3+ caused a modest enhancement of activity. EDTA-Fe3+ greatly stimulated NADPH-cytochrome P450 reductase-catalyzed peroxidation of liposomes with ADP-Fe3+. In contrast, the addition of EDTA, rather than EDTA-Fe3+ inhibited the liposomal peroxidation catalyzed by either enzyme with ADP-Fe3+ when the EDTA concentration exceeded the concentration of Fe3+. 相似文献