全文获取类型
收费全文 | 5361篇 |
免费 | 383篇 |
国内免费 | 1篇 |
专业分类
5745篇 |
出版年
2023年 | 38篇 |
2022年 | 96篇 |
2021年 | 152篇 |
2020年 | 103篇 |
2019年 | 145篇 |
2018年 | 211篇 |
2017年 | 172篇 |
2016年 | 210篇 |
2015年 | 268篇 |
2014年 | 294篇 |
2013年 | 410篇 |
2012年 | 405篇 |
2011年 | 451篇 |
2010年 | 304篇 |
2009年 | 251篇 |
2008年 | 236篇 |
2007年 | 235篇 |
2006年 | 181篇 |
2005年 | 162篇 |
2004年 | 129篇 |
2003年 | 127篇 |
2002年 | 111篇 |
2001年 | 94篇 |
2000年 | 117篇 |
1999年 | 82篇 |
1998年 | 64篇 |
1997年 | 32篇 |
1996年 | 38篇 |
1995年 | 30篇 |
1994年 | 17篇 |
1993年 | 22篇 |
1992年 | 24篇 |
1991年 | 26篇 |
1990年 | 16篇 |
1989年 | 28篇 |
1988年 | 17篇 |
1987年 | 16篇 |
1986年 | 23篇 |
1985年 | 20篇 |
1984年 | 31篇 |
1983年 | 24篇 |
1982年 | 26篇 |
1981年 | 18篇 |
1980年 | 39篇 |
1979年 | 31篇 |
1978年 | 31篇 |
1977年 | 28篇 |
1976年 | 16篇 |
1975年 | 16篇 |
1974年 | 13篇 |
排序方式: 共有5745条查询结果,搜索用时 15 毫秒
21.
The mixed bis(arylhydrazones) of l-threo-2,3-hexodiulosono-1,4-lactone rearrange into pyrazolediones. Mono- and bis-(arylhydrazones) of isoascorbic acid were prepared; the latter are present in two forms that afford the same pyrazoledione. Acetylation, benzoylation, and periodate oxidation of these pyrazolediones were studied, and some condensation products from the pyrazole aldehyde were prepared. Some of the i.r. and mass-spectral data were discussed. 相似文献
22.
l-threo-2,3-Hexodiulosono-1,4-lactone 2-(arylhydrazones) (2) were prepared by condensation of dehydro-l-ascorbic acid with various arylhydrazines. Reaction of 2 with hydroxylamine gave the 2-(arylhydrazone) 3-oximes (3). On boiling with acetic anhydride, 3 gave 2-aryl-4-(2,3-di-O-acetyl-l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxylic acid 5,41-lactones (4). On treatment of 4 with liquid ammonia, 2-aryl-4-(l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxamides (5) were obtained. Acetylation of 5 with acetic anhydride-pyridine gave the triacetates, and vigorous acetylation with boiling acetic anhydride gave the tetraacetyl derivatives. Periodate oxidation of 5 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxamides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamides, characterized as the monoacetates and diacetates. Controlled reaction of 2 with sodium hydroxide, followed by neutralization, gave 3-(l-threo-glycerol-l-yl)-4,5-isoxazolinedione 4-(arylhydrazones), characterized by their triacetates. Reaction of 2 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy-l-threo-2,3-hexodiulosono-1,4-lactone 2-(arylhydrazones); these were converted into 4-(2-O-acetyl-3-bromo-3-deoxy-l-threo-glycerol-l-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,41-lactones on treatment with acetic anhydride-pyridine. 相似文献
23.
Christophe Biju-Duval Hajer Ennafaa Nicole Dennebouy Monique Monnerot Françoise Mignotte Ramon C. Soriguer Amel El Gaaïed Ali El Hili Jean-Claude Mounolou 《Journal of molecular evolution》1991,33(1):92-102
Summary A characterization was conducted on mitochondrial DNA (mtDNA) molecules extracted separately from 107 European rabbits (Oryctolagus cuniculus) both wild and domestic, 13 European hares (Lepus capensis), and 1 eastern cottontail (Sylvilagus floridanus). Experimentally this study took into account restriction site polymorphism, overall length variation of the noncoding region, and numbers of repeated sequences. Nucleotide divergences indicate that the mtDNAs from the three species derived from a common ancestor some 6–8 million years (Myr) ago. Every animal appeared heteroplasmic for a set of molecules with various lengths of the noncoding region and variable numbers of repeated sequences that contribute to them. This systematic heteroplasmy, most probably generated by a rate of localized mtDNA rearrangements high enough to counterbalance the cellular segregation of rearranged molecules, is a shared derived character of leporids.The geographic distribution of mtDNA polymorphism among wild rabbit populations over the western European basin shows that two molecular lineages are represented, one in southern Spain, the second over northern Spain, France, and Tunisia. These two lineages derived from a common ancestor some 2 Myr ago. Their present geographical distribution may be correlated to the separation of rabbits into two stocks at the time of Mindel glaciation.Finally the distribution of mtDNA diversity exhibits a mosaic pattern both at inter- and intrapopulation levels. 相似文献
24.
Aline Frville Bndicte Gnangnon Annie Z. Tremp Caroline De Witte Katia Cailliau Alain Martoriati El Moukthar Aliouat Priyanka Fernandes Cerina Chhuon Olivier Silvie Sabrina Marion Ida Chiara Guerrera Johannes T. Dessens Christine Pierrot Jamal Khalife 《Open biology》2022,12(8)
Protein phosphatase 1 (PP1) is a key enzyme for Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. Here, we report the functional characterization of the Plasmodium berghei leucine-rich repeat protein 1 (PbLRR1), an orthologue of SDS22, one of the most ancient and conserved PP1 interactors. Our study shows that PbLRR1 is expressed during intra-erythrocytic development of the parasite, and up to the zygote stage in mosquitoes. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and inhibits its phosphatase activity. Genetic analysis demonstrates that PbLRR1 depletion adversely affects the development of oocysts. PbLRR1 interactome analysis associated with phospho-proteomics studies identifies several novel putative PbLRR1/PbPP1 partners. Some of these partners have previously been characterized as essential for the parasite sexual development. Interestingly, and for the first time, Inhibitor 3 (I3), a well-known and direct interactant of Plasmodium PP1, was found to be drastically hypophosphorylated in PbLRR1-depleted parasites. These data, along with the detection of I3 with PP1 in the LRR1 interactome, strongly suggest that the phosphorylation status of PbI3 is under the control of the PP1–LRR1 complex and could contribute (in)directly to oocyst development. This study provides new insights into previously unrecognized PbPP1 fine regulation of Plasmodium oocyst development through its interaction with PbLRR1. 相似文献
25.
El Ghazi I Martin BL Armitage IM 《Experimental biology and medicine (Maywood, N.J.)》2006,231(9):1500-1506
Metallothionein (MT)-3, originally called growth inhibitory factor (GIF), was initially identified through its ability to inhibit the growth of neuronal cells in the presence of brain extract. MT-3 is the brain specific isoform of the MT family whose specific biological activity associates it with neurological disorders. Indeed, studies report that MT-3 is decreased by ~30% in brains of patients with Alzheimer disease (AD). Furthermore, many lines of evidence suggest that MT-3 engages in specific protein interactions. To address this, we conducted immunoaffinity chromatography experiments using an immobilized anti-mouse MT-3 antibody. We identified five associated proteins from the pool of sixteen recovered using mass spectrometry and tandem mass spectrometry after in-gel trypsin digestion of bands from the affinity chromatography. The proteins identified were: heat shock protein 84 (HSP84), heat shock protein 70 (HSP70), dihydropyrimidinase-like protein-2 (DRP-2), creatine kinase (CK) and beta-actin. Coimmunoprecipitation experiments, also conducted on whole mouse brain extract using the anti-mouse MT-3 antibody along with commercially available antibodies against HSP84 and CK, confirmed that these three proteins were in a single protein complex. Immunohistochemical experiments were then conducted on the perfused mouse brain that confirmed the in situ colocalization of CK and MT-3 in the hippocampus region. These data provide new insights into the involvement of MT-3 in a multiprotein complex, which will be used to understand the biological activity of MT-3 and its role in neurological disease. 相似文献
26.
Biotransformation of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide,a novel potent 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties: In vitro and in silico approach 下载免费PDF全文
Karolina Słoczyńska Katarzyna Wójcik‐Pszczoła Vittorio Canale Paweł Żmudzki Paweł Zajdel Elżbieta Pękala 《Journal of biochemical and molecular toxicology》2018,32(5)
The aim of the study was to investigate the metabolism of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide (PZ‐1150), a novel 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties, by the following three ways: in vitro with microsomes; in vitro employing Cunninghamella echinulata, and in silico using MetaSite. Biotransformation of PZ‐1150 with microsomes resulted in five metabolites, while transformation with C. echinulata afforded two metabolites. In both models, the predominant metabolite occurred due to hydroxylation of benzene ring. In silico data coincide with in vitro experiments, as three MetaSite metabolites matched compounds identified in microsomal samples. In human liver microsomes PZ‐1150 exhibited in vitro half‐life of 64 min, with microsomal intrinsic clearance of 54.1 μL/min/mg and intrinsic clearance of 48.7 mL/min/kg. Therefore, PZ‐1150 is predicted to be a high‐clearance agent. The study demonstrated the applicability of using microsomal model coupled with microbial model to elucidate the metabolic pathways of compounds and comparison with in silico metabolite predictions. 相似文献
27.
Hanna Grajek Regina Drabent Grażyna Żurkowska Czesław Bojarski 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,801(3):456-460
The electronic absorption spectra of the flavomononucleotide (FMN) in aqueous solution and in glycerine-water solution with change of the dye concentration have been measured. The FMN dimer absorption spectrum, monomer absorption spectrum, dimerization constant K and molar fraction of the monomer were calculated. It was found that FMN dimerization constants in aqueous solution were Ka = 118.0 l/mol and in glycerine Kg = 20.5 l/mol. In the region of the monomer absorption band two dimer absorption bands appear, in accordance with the Kasha molecular exciton theory. 相似文献
28.
Twelve mature wethers were used in an experiment of change-over design to determine the effect of complete diet feeding on intake and digestibility of diets based on alkalitreated straw and a concentrate containing rolled barley and extracted soya bean meal. Two diets were used: D1 with a 50:50, and D2 with a 75:25 ratio of straw:concentrates on a dry matter basis. The straw and concentrates of each diet were given either separately (S) or as a complete diet (C). Complete diets gave a slightly, but not significantly higher intake (C, 86.5) and S, 82.5 g dry matter /kg W0.75 per day). The separate method gave a significantly higher digestibility coefficient for dry matter (C, 62.2 and S, 65.5; P < 0.05) and for crude fibre (C, 57.2 and S, 62.5; P < 0.01). Water intake increased by 42.7 ml g?1 Na derived from NaOH. There were no significant interactions between the method of feeding and the type of diet in intake and digestibility of the diets or in the intake of water. 相似文献
29.
Farag Ola M. Abd-Elsalam Reham M. Ogaly Hanan A. Ali Sara E. El Badawy Shymaa A. Alsherbiny Muhammed A. Li Chun Guang Ahmed Kawkab A. 《Neurochemical research》2021,46(4):819-842
Neurochemical Research - Acrylamide (ACR) is an environmental pollutant with well-demonstrated neurotoxic and neurodegenerative effects in both humans and experimental animals. The present study... 相似文献
30.
Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit hyperproliferation and overexpression of cell cycle proteins. We earlier showed that small peptide fragments of cytoplasmic domain of natriuretic receptor-C (NPR-C) attenuate vasoactive peptide-induced hyperproliferation of VSMC. The present study investigated if C-ANP4–23, a specific agonist of NPR-C, could attanuate the hyperproliferation of VSMC from SHR by inhibiting the overexpression of cell cycle proteins and examine the underlying signaling pathways contributing to this inhibition. The proliferation of VSMC was determined by [3H] thymidine incorporation and the expression of proteins was determined by Western blotting. The hyperproliferation of VSMC from SHR and overexpression of cyclin D1,cyclin A, cyclin E, cyclin-dependent kinase 2 (cdk2), phosphorylated retinoblastoma protein (pRb), Giα proteins and enhanced phosphorylation of ERK1/2 and AKT exhibited by VSMC from SHR were attenuated by C-ANP4–23 to control levels. In addition, in vivo treatment of SHR with C-ANP4–23 also attenuated the enhanced proliferation of VSMC. Furthemore, PD98059, wortmannin and pertussis toxin, the inhibitors of MAP kinase, PI3kinase and Giα proteins respectively, also attenuated the hyperproliferation of VSMC from SHR and overexpression of cell cycle proteins to control levels. These results indicate that NPR-C activation by C-ANP4–23 attenuates the enhanced levels of cell cycle proteins through the inhibition of enhanced expression of Giα proteins and enhanced activation of MAPkinase/PI3kinase and results in the attenuation of hyperproliferation of VSMC from SHR. It may be suggested that C-ANP4–23 could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension, atherosclerosis and restenosis. 相似文献