全文获取类型
收费全文 | 1530篇 |
免费 | 11篇 |
国内免费 | 15篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 40篇 |
2019年 | 84篇 |
2018年 | 81篇 |
2017年 | 63篇 |
2016年 | 56篇 |
2015年 | 29篇 |
2014年 | 124篇 |
2013年 | 157篇 |
2012年 | 98篇 |
2011年 | 175篇 |
2010年 | 114篇 |
2009年 | 61篇 |
2008年 | 42篇 |
2007年 | 56篇 |
2006年 | 62篇 |
2005年 | 52篇 |
2004年 | 32篇 |
2003年 | 39篇 |
2002年 | 14篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 9篇 |
1998年 | 3篇 |
1997年 | 15篇 |
1996年 | 16篇 |
1995年 | 13篇 |
1994年 | 11篇 |
1993年 | 11篇 |
1992年 | 11篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1978年 | 3篇 |
1976年 | 6篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有1556条查询结果,搜索用时 281 毫秒
1.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-7):601-605
A novel approach for the synthesis of 5′-capped 2′-O-methyloligoribonucleotides on a disulfide-tethered solid support is described. The key step of the synthesis is ZnCl2 promoted coupling of m7GDP imidazolide to a fully deprotected oligonucleotide 5′-phosphate on-support. By this methodology m7G5′pppm2′Apm2′Upm2′Ap has been prepared. 相似文献
2.
3.
《Bioorganic & medicinal chemistry letters》2014,24(18):4533-4537
N-Acetylglucosaminyltransferase (GnT) III is a glycosyltransferase which produces bisected N-glycans by transferring GlcNAc to the 4-position of core mannose. Bisected N-glycans are involved in physiological and pathological processes through the functional regulation of their carrier proteins. An understanding of the biological functions of bisected glycans will be greatly accelerated by use of specific inhibitors of GnT-III. Thus far, however, such inhibitors have not been developed and even the substrate-binding mode of GnT-III is not fully understood. To gain insight into structural features required of the substrate, we systematically synthesized four N-glycan units, the branching parts of the bisected and non-bisected N-glycans. The series of syntheses were achieved from a common core trimannose, giving bisected tetra- and hexasaccharides as well as non-bisected tri- and pentasaccharides. A competitive GnT-III inhibition assay using the synthetic substrates revealed a vital role for the Manβ(1–4)GlcNAc moiety. In keeping with previous reports, GlcNAc at the α1,3-branch is also involved in the interaction. The structural requirements of GnT-III elucidated in this study will provide a basis for rational inhibitor design. 相似文献
4.
A series of thirty (30) thiazole analogs were prepared, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC50 value ranging between 1.59 ± 0.01 and 389.25 ± 1.75 μM when compared with the standard eserine (IC50, 0.85 ± 0.0001 μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC50 values 1.59 ± 0.01, 1.77 ± 0.01, 6.21 ± 0.01, 7.56 ± 0.01, 8.46 ± 0.01, 14.81 ± 0.32 and 16.54 ± 0.21 μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3 ± 0.50, 35.3 ± 0.64, 36.6 ± 0.70, 44.81 ± 0.81, 46.36 ± 0.84, 48.2 ± 0.06 and 48.72 ± 0.91 μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking. 相似文献
5.
Minhang Xin 《Steroids》2010,75(1):53-7742
An efficient and practical scheme to synthesize 2-methoxyestradiol has been developed. The key step was the copper-mediated methoxylation using ethyl acetate as a co-catalyst to introduce a methoxyl group. These synthetic procedures of four steps from 17β-estradiol as starting material gave 2-methoxyestradiol with a 61% overall yield. 相似文献
6.
Kinetics of Drug-Induced Changes in Dopamine and Serotonin Metabolite Concentrations in the CSF of the Rat 总被引:5,自引:4,他引:1
Cerebrospinal fluid (CSF) was removed at a constant flow rate of 1 microliter/min from the third ventricle of anesthetized rats. Every 15 min, CSF dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined by direct injection of CSF into a liquid chromatographic system coupled with electrochemical detection. Mean CSF concentrations of DOPAC, HVA, and 5-HIAA were 1.29 microM, 0.88 microM, and 2.00 microM, respectively. In order to determine the turnover rates of dopamine (DA) and serotonin, experiments using monoamine oxidase (MAO) inhibition were performed. Tranylcypromine (20 mg/kg i.p.) induced a sharp exponential decrease of CSF DOPAC, HVA, and 5-HIAA, with respective half-lives of 15.60 min, 16.91 min, and 77.23 min. Their respective turnover rates were 3.74, 2.22, and 1.18 nmol X ml-1 X h-1. m-Hydroxybenzylhydrazine (NSD-1015, 100 mg/kg i.p.) and monofluoromethyl-DOPA (100 mg/kg i.p.), two decarboxylase inhibitors, induced a slow exponential decrease of all three CSF metabolites. alpha-Methyl-p-tyrosine (250 mg/kg i.p.) also induced a slow exponential decrease of DOPAC and HVA. These decreases of CSF DOPAC and HVA induced by DA synthesis inhibitors may reflect the turnover of DA in vivo. Haloperidol (0.5 mg/kg i.p.) considerably enhanced CSF DOPAC and HVA without affecting 5-HIAA, confirming that dopaminergic receptors modulate DA neurotransmission in vivo. Haloperidol administered 1.5 h after NSD-1015 did not increase DOPAC and HVA, in contrast to reserpine (5 mg/kg i.p.) injected under the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
7.
Abidin Bin Hamid John E. Smith 《Journal of industrial microbiology & biotechnology》1987,2(3):137-141
Summary Phenobarbital stimulated aflatoxin biosynthesis byAspergillus flavus and this was paralleled by an increase in microsomal NADPH-cytochromeP-450 reductase and cytochromeP-450 activities. Aflatoxin biosynthesis was inhibited by SKF 525-A, metyrapone and cyanide, inhibitors of the cytochromeP-450 monooxygenase system, further suggesting that aflatoxin biosynthesis byA. flavus could be mediated by a cytochromeP-450 monooxygenase enzyme system. 相似文献
8.
The kinetics of asymbiotic nitrogenase activity in three strains of the actinomycete Frankia were studied. Decay rates for enzyme activity were determined by adding chloramphenicol to active acetylene-reducing cells and measuring the time required for all activity to cease. Synthesis rates were measured by bubbling oxygen through actively-reducing cells (which totally destroyed all activity) and then measuring the time required for activity to return to normal. Decay rates (t
1/2) for these three strains were approximately 30 to 40 min. Synthesis rates were slower and initial nitrogenase activities were recorded about 110 min (DDB 011610) or 210 min (DDB 020210 and WgCc1.17) after return to air-equilibrated cultures. Frankia strain WgCc1.17 showed a greater sensitivity to oxygen and nitrogenase activity was totally lost when cells were bubbled only with atmospheric concentrations of oxygen. The results presented here indicate that nitrogenase activity turnover time is relatively rapid, on the order of minutes rather than hours or days. However, regulation of nitrogenase activity will differ from one strain to another and asmmbiotic characterization will be useful for understanding nitrogenase regulation in the bacterial-plant symbiosis.Contribution no. 879 from the Battelle-Kettering Laboratory 相似文献
9.
On the Significance of Tyrosine for the Synthesis and Catabolism of Dopamine in Rat Brain: Evaluation by HPLC with Electrochemical Detection 总被引:8,自引:5,他引:3
Abstract: A chemical assay of tyrosine (Tyr) in nervous tissue is described. The method is based on a rapidly performed isolation of Tyr on small Sephadex G 10 columns, followed by reverse-phase HPLC in conjunction with amperometric detection. The method permitted the additional quantification of 3,4-dihydroxyphenylalanine, dopamine (DA), and its acidic metabolites. The method was applied to a study of the effects of γ-butyrolactone, haloperidol, haloperidol in combination with amfonelic acid, morphine, NSD 1015, and tyrosine methylester on the concentration of Tyr in the striatum, frontal cortex, hypothalamus, and cerebellum of rat brain. The effect of tyrosine methylester on DA and its acidic metabolites was investigated in the striatum and frontal cortex. Morphine and NSD 1015 were found to increase Tyr levels. γ-Butyrolactone, haloperidol, and haloperidol combined with amfonelic acid decreased the Tyr content in a manner related to their stimulatory effect on DA biosynthesis. These effects were restricted to DA-rich brain areas. It was concluded that during conditions of increased DA biosynthesis, the Tyr pool still possesses a considerable reserve capacity. The results bring into question the concept that brain Tyr is an important additional factor controlling catechol synthesis during increased tyrosine hydroxylase activity. 相似文献
10.
Summary The ultrastructure of the haematopoietic cells in the polychaetes Neoamphitrite figulus Dalyell, Lanice conchilega (Pallas), Arenicola marina (L.), Myxicola infundibulum Renier, Megalomma vesiculusom (Montagu), Sabella penicillus L., are compared: all show similarities in having well developed Golgi, granular endoplasmic reticulum and haemoglobin or chlorocruorin in vesicles, and numerous mitochondria. The porphyrin byproducts of synthesis are combined with iron as haematins within electrondense granules built up from multi-lamellar organelles. The structure of the basal lamina which alone separates the cells from the lumen of the vessels is described and evidence is presented for the method of release of the haem into the plasma by reverse pinocytosis. The cycle of synthesis within the cell is discussed and the process of haem synthesis in annelids is reviewed. The structure of the haemoglobin-containing coelomocytes of Neoamphitrite figulus is briefly described.This work was made possible by an award from the Science Research Council. We would also like to thank the Director and Staff of the Plymouth Laboratory, where some of the work was done, for their hospitality and facilities. 相似文献