全文获取类型
收费全文 | 571篇 |
免费 | 21篇 |
国内免费 | 16篇 |
专业分类
608篇 |
出版年
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 4篇 |
2020年 | 10篇 |
2019年 | 26篇 |
2018年 | 16篇 |
2017年 | 16篇 |
2016年 | 20篇 |
2015年 | 12篇 |
2014年 | 29篇 |
2013年 | 67篇 |
2012年 | 15篇 |
2011年 | 30篇 |
2010年 | 14篇 |
2009年 | 22篇 |
2008年 | 21篇 |
2007年 | 33篇 |
2006年 | 16篇 |
2005年 | 15篇 |
2004年 | 23篇 |
2003年 | 21篇 |
2002年 | 22篇 |
2001年 | 13篇 |
2000年 | 6篇 |
1999年 | 10篇 |
1998年 | 9篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 7篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 11篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1950年 | 1篇 |
排序方式: 共有608条查询结果,搜索用时 10 毫秒
21.
黑色素合成是桦褐孔菌Phaeoporus obliquus次生代谢过程中的一个重要事件。黑色素的过多合成势必影响其他酚类的积累。本文以茉莉酸和双氧水为调控因子,开展了该突变体深层发酵过程酚类化合物积累研究。正常培养条件下,每升发酵液积累酚类化合物最高可达317.45mg/L,其中包括苯甲酸衍生物(45.3mg/L),黄酮苷元(74.4mg/L),黄酮苷(160mg/L)以及硬毛素类化合物(18.5mg/L)。加入茉莉酸后,总酚最大值增加到620.45mg/L,其中苯甲酸衍生物增加到230.26mg/L,黄酮苷元增加到166.86mg/L,而黄酮苷和硬毛素类化合物却分别降低到98.5mg/L和7.1mg,双氧水的加入没有提高总酚的最大积累(315.69mg/L)。因此,与野生型相比,黑色素缺失使总酚的积累有所增加,随茉莉L酸的加入总酚积累最大值增加近一倍。虽然双氧水的加入提高了苯丙氨酸裂解酶活性,但总酚的积累却没有增加,这可能是由于一部分酚类化合物在抗双氧水氧化胁迫过程中被消耗。 相似文献
22.
A spectroscopic examination of six galactonoamidines with inhibition constants and efficacy in the low nanomolar concentration range (Ki = 6–11 nM, IC50 = 12–36 nM) suggested only two of them as putative transition state analogs for the hydrolysis of β-galactosides by β-galactosidase (A. oryzae). A rationale for the experimental results was elaborated using docking and molecular dynamics studies. An analysis of the combined observations reveals several common factors of the compounds suggested as transition state analogs (TSAs): the putative TSAs have a similar orientation in the active site; show conserved positioning of the glycon; display a large number of H-bond interactions toward the catalytically active amino acid residues via their glycon; and exhibit hydrophobic interactions at the outer rim of the active site with small changes of the position and orientation of their respective aglycons. 相似文献
23.
24.
Bing Zhu Yuanzhen Dong Jie Ma Minwei Chen Sida Ruan Wenjie Zhao Jun Feng 《Journal of peptide science》2020,26(11)
Presently, echinocandins have been recommended as the first‐line drugs for the treatment of invasive candidiasis. However, low oral bioavailability and solubility limit their application. To improve this situation, this study chose amino acid and fatty acid as raw materials to modify the nucleus of echinocandin B. Six N‐acylated analogs were screened from the derivatives that possessed potent antifungal activity and good water solubility. Based on antifungal susceptibility and hemolytic toxicity, compound 5 as the candidate had good antifungal activity and no hemolytic effect. Moreover, compared with anidulafungin, compound 5 showed a comparable fungicidal effect, much higher solubility, and lower toxicity. In conclusion, compound 5 has the potential for further research and development on account of reserved antifungal activity, high solubility, and low toxicity. 相似文献
25.
《Nucleosides, nucleotides & nucleic acids》2013,32(5):777-787
In line with the paradigm, that antisense oligonucleotides should contain minimal structural modifications, in order to minimize the risk of toxicity and antigenicity, we describe here the preparation and the properties of oligonucleotides modified to contain, in addition to phosphodiester bonds, a small number of phosphoramidate internucleotide linkages substituted with aminoethoxyethyl groups in order to convey protection against exo‐ and endonucleases. Prolonged stability was, in fact, found in model experiments with respective enzymes, as well as in studies done in human blood serum. Regardless of number and position of phosphoramidate linkages, the modified oligonucleotides showed only a slight decrease of Tm in hybridization studies with complementary oligonucleotides. 相似文献
26.
27.
Godefridus J. Peters Auke D. Adema Irene V. Bijnsdorp Marit L. Sandvold 《Nucleosides, nucleotides & nucleic acids》2013,32(12):1168-1180
Many drugs that are currently used for the treatment of cancer have limitations, such as induction of resistance and/or poor biological half-life, which reduce their clinical efficacy. To overcome these limitations, several strategies have been explored. Chemical modification by the attachment of lipophilic moieties to (deoxy)nucleoside analogs should enhance the plasma half-life, change the biodistribution, and improve cellular uptake of the drug. Attachment of a lipophilic moiety to a phosphorylated (deoxy)nucleoside analog will improve the activity of the drugs by circumventing the rate-limiting activation step of (deoxy)nucleoside analogs. Encapsulating drugs in nanoparticles or liposomes protects the drug against enzymatic breakdown in the plasma and makes it possible to get lipophilic compounds to the tumor site. In this review, we discuss the considerable progress that has been made in increasing the efficacy of classic (deoxy)nucleoside and fluoropyrimidine compounds by chemical modifications and alternative delivery systems. 相似文献
28.
Abstract A procedure was developed for the chemical synthesis of P1,P2-dinucleoside-5′-diphosphates (N1(5′)pp(5′)N2) on a nanomolar scale Reaction conditions for activating purine-5′-monophosphates (pA, pG, and pm7G) by 1,1′-carbonyldiimidazole were studied and optimized in respect to solvents and amount of activating reagent used. Various dinucleoside-5′-diphosphates were synthesized in 62-98% yield by incubating activated and non-activated purine-5′-monophosphates. Two unexpected by-products were formed by competition reactions: the imidazolidate of the non-activated nucleotide and the corresponding symmetrically substituted dinucleoside-5′-diphosphate. A mechanism is proposed to explain the observed side reactions. 相似文献
29.
Muhammad Murtaza Hassan Ayat Yaseen Abdelaziz Ebead Gerald Audette 《Nucleosides, nucleotides & nucleic acids》2013,32(9):518-531
AbstractA synthesis of cyclobutene nucleoside analogs in which the nucleobase is tethered by a methylene group is described. The coupling of 6-chloropurine with 3-hydroxymethyl-cyclobutanone proceeds via its triflate to give both N-7 and N-9 regioisomers with relative yields corresponding to the calculated charge distribution of the 6-chloropurinyl anion. The stereoselective reduction of the N-alkylated ketones yielded quantitatively one stereoisomer in each case. The structural assignments were based on spectroscopic data and single crystal X-ray diffraction. Attempts to photoexcite the N-7 and N-9 ketones in order to promote ring-expansion did not ensue. Preliminary evidence suggests a photodecarbonylation to cyclopropanes took place. 相似文献
30.
Derong Ding Justin R. Nickell Agripina G. Deaciuc Narsimha Reddy Penthala Linda P. Dwoskin Peter A. Crooks 《Bioorganic & medicinal chemistry》2013,21(21):6771-6777
Lobelane analogs that incorporate a central piperidine or pyrrolidine moiety have previously been reported by our group as potent inhibitors of VMAT2 function. Further central ring size reduction of the piperidine moiety in lobelane to a four-membered heterocyclic ring has been carried out in the current study to afford novel cis-and trans-azetidine analogs. These azetidine analogs (15a–15c and 22a–22c) potently inhibited [3H]dopamine (DA) uptake into isolated synaptic vesicles (Ki ? 66 nM). The cis-4-methoxy analog 22b was the most potent inhibitor (Ki = 24 nM), and was twofold more potent that either lobelane (2a, Ki = 45 nM) or norlobelane (2b, Ki = 43 nM). The trans-methylenedioxy analog, 15c (Ki = 31 nM), was equipotent with the cis-analog, 22b, in this assay. Thus, cis- and trans-azetidine analogs 22b and 15c represent potential leads in the discovery of new clinical candidates for the treatment of methamphetamine abuse. 相似文献