全文获取类型
收费全文 | 2326篇 |
免费 | 67篇 |
国内免费 | 26篇 |
出版年
2023年 | 26篇 |
2022年 | 23篇 |
2021年 | 35篇 |
2020年 | 77篇 |
2019年 | 125篇 |
2018年 | 122篇 |
2017年 | 101篇 |
2016年 | 90篇 |
2015年 | 43篇 |
2014年 | 131篇 |
2013年 | 238篇 |
2012年 | 32篇 |
2011年 | 102篇 |
2010年 | 52篇 |
2009年 | 79篇 |
2008年 | 81篇 |
2007年 | 79篇 |
2006年 | 84篇 |
2005年 | 50篇 |
2004年 | 52篇 |
2003年 | 55篇 |
2002年 | 48篇 |
2001年 | 19篇 |
2000年 | 16篇 |
1999年 | 20篇 |
1998年 | 23篇 |
1997年 | 25篇 |
1996年 | 17篇 |
1995年 | 19篇 |
1994年 | 23篇 |
1993年 | 17篇 |
1992年 | 25篇 |
1991年 | 15篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1987年 | 8篇 |
1986年 | 6篇 |
1985年 | 55篇 |
1984年 | 54篇 |
1983年 | 21篇 |
1982年 | 48篇 |
1981年 | 43篇 |
1980年 | 54篇 |
1979年 | 50篇 |
1978年 | 36篇 |
1977年 | 25篇 |
1976年 | 17篇 |
1975年 | 10篇 |
1973年 | 16篇 |
排序方式: 共有2419条查询结果,搜索用时 296 毫秒
191.
192.
A novel series of 3,5,6‐trimethylpyrazine‐2‐methoxy (or methylamino) substituted benzoyl‐guanidine derivatives were designed and synthesized as Na+/H+ exchange (NHE) inhibitors. In this study, compounds with electron‐withdrawing substituents on the benzene ring seemed to improve NHE‐1 inhibitory activities. Compounds 6d, 6k , and 6l were found to be potent inhibitors of NHE‐1 (IC50=3.0±1.6, 3.0±1.4, and 1.6±0.4 nmol/l, resp.). Furthermore, they showed a remarkable reduction of infarct size in the rat myocardial infarction model in vivo. 相似文献
193.
The purpose of this study was to assess the natural exposure of male horses (Equus caballus) to the mycotoxin zearalenone (ZEA) by using the ELISA test and to evaluate the effects of in vitro exposure of sperm cells to mycotoxin-containing urine extracts on sperm chromatin structure stability. Because of their occurrence in urine samples, ZEA and its derivatives were tested by sperm chromatin structure assay (SCSA) at natural levels detected by ELISA. Thirty-eight urine extracts of Italian (n = 11) and northeastern European (n = 27) horses were tested on frozen-thawed spermatozoa to evaluate the toxic effect of mycotoxin on their chromatin structure by flow cytometry. Different parameters of the DNA fragmentation index (DFI), such as the mean (), the percentage (%-DFI), and the standard deviation (SD-DFI), were analyzed. Urine samples showed a mean level of 32.3 ng/mL ZEA with significantly higher concentrations in northeastern European samples than in Italian samples, probably in relation to climatic and feeding differences. The toxic effects of ZEA-containing urine samples on SCSA parameters were found at low ZEA concentrations and were mainly observed in Italian samples. By using mycotoxin standards, ZEA, α-zearalenol, and β-zearalenol proved to be more toxic compounds for sperm chromatin stability than other tested derivatives. A nongenomic mechanism of action can be hypothesized. 相似文献
194.
Anne Sofie Busk Heitmann Ali Asghar Hakami Zanjani Martin Berg Klenow Anna Mularski Stine Lauritzen Snder Frederik Wendelboe Lund Theresa Louise Boye Catarina Dias Poul Martin Bendix Adam Cohen Simonsen Himanshu Khandelia Jesper Nylandsted 《The Journal of biological chemistry》2021,297(2)
Repair of damaged plasma membrane in eukaryotic cells is largely dependent on the binding of annexin repair proteins to phospholipids. Changing the biophysical properties of the plasma membrane may provide means to compromise annexin-mediated repair and sensitize cells to injury. Since, cancer cells experience heightened membrane stress and are more dependent on efficient plasma membrane repair, inhibiting repair may provide approaches to sensitize cancer cells to plasma membrane damage and cell death. Here, we show that derivatives of phenothiazines, which have widespread use in the fields of psychiatry and allergy treatment, strongly sensitize cancer cells to mechanical-, chemical-, and heat-induced injury by inhibiting annexin-mediated plasma membrane repair. Using a combination of cell biology, biophysics, and computer simulations, we show that trifluoperazine acts by thinning the membrane bilayer, making it more fragile and prone to ruptures. Secondly, it decreases annexin binding by compromising the lateral diffusion of phosphatidylserine, inhibiting the ability of annexins to curve and shape membranes, which is essential for their function in plasma membrane repair. Our results reveal a novel avenue to target cancer cells by compromising plasma membrane repair in combination with noninvasive approaches that induce membrane injuries. 相似文献
195.
A soluble enzyme, extracted from tobacco cell-suspension cultures 24 h after treatment with 100 μM methyl jasmonate, has been shown to synthesize acetovanillone (apocynin) from feruloyl-CoA in the presence of NAD. The enzyme displayed Michaelis-Menten kinetics with apparent Km values of 5.6 μM for feruloyl-CoA and 260 μM for NAD and exhibited very high specificity for its substrates. The increase in acetovanillone synthase activity was followed by an increase in the concentration of both acetovanillone and acetosyringone in the culture medium. No intermediate could be detected when analysing the reaction medium by HPLC during the formation of acetovanillone in cell-free extracts. The apparent molecular mass estimated by gel permeation on an FPLC column was ca. 79 kDa. To our knowledge, this is the first report of an enzymic system catalysing the synthesis of an acetophenone. This work demonstrates that the biosynthesis of acetophenones in tobacco proceeds from hydroxycinnamic acids through a CoA-dependent β-oxidation pathway. Interestingly in methyl jasmonate-treated cells, which synthesize very large amounts of hydroxycinnamoylputrescines, inhibition of the synthesis of these conjugates increased the concentration of acetovanillone and acetosyringone in the culture medium, suggesting that the two metabolic pathways can compete for their common precursors, i.e. hydroxycinnamoyl-CoA thioesters. 相似文献
196.
17α-substituted ethynylestradiols, derived from estrone, were converted to their corresponding 17α-(bromo- or iodo-propargyl)estrone intermediates. Nucleophilic substitution onto these moieties with malonate diester followed by hydrolysis and complexation with cis-Pt(Me2en)I2 (Me2en = N,N-dimethylethylenediamine) gave cis-Pt(Me2en)(2-(3-(17β-estradiol-17α-yl)-prop-2-ynyl)malonato) 7, thus demonstrating that these estrogen-derived compounds can be used to synthesize stable Pt(II) complexes. The 3-(17β-estradiol-17α-yl)-prop-2-ynyl-1-sulfanylethylthiol 23 was also prepared. 相似文献
197.
The aerial parts of Symphyopappus compressus afrorded three new kolavane derivatives and those of S. reticulatus ten diterpenes of this type, two of them esterified with long chain fatty acids. Furthermore, a dihydroxyphenylpropanol, also esterified with long chain fatty acids, was present in both species. The roots of S. reticulatus afforded a new tremetone derivative. The structures were elucidated by spectroscopic methods and some chemical transformations. 相似文献
198.
E. Renbutsu S. Okabe Y. Omura F. Nakatsubo S. Minami H. Saimoto Y. Shigemasa 《Carbohydrate polymers》2007,69(4):697-706
Novel chitosan derivatives with UV-curable functional groups, such as 3-methoxy-4-(2-hydroxy-3-methacryloyloxypropoxy)benzyl, 3,4-bis(2-hydroxy-3-methacryloyloxypropoxy)benzyl, 3-methoxy-4-methacryloyloxybenzyl, and 3,5-dimethacryloyloxybenzyl groups, were prepared. Introduction of photosensitive functional groups to chitosan was accomplished by reductive N-alkylation via Schiff’s bases using corresponding photosensitive aldehydes. Compared to starting chitosan, UV-curable chitosan derivatives showed better solubility in several organic solvents, such as DMSO and 70% methacrylic acid. The solubility of these compounds increased with an increase in the degree of substitution of the N-alkyl side chains. After UV irradiation for 20 s under a high-pressure mercury lamp at a distance of 15 cm from the samples, acidic methanol solutions of these derivatives were transformed to gels in the presence of photo-initiator, and their dried films adsorbed palladium (II) at pH 1.1 and pH 5.3. The UV-curable chitosan derivatives were successfully used as coating materials for electroless plating on non-conductive substances. 相似文献
199.
16Beta-aminomethyl-17beta-hydroxyestrone 3-methyl ether 6 and its N-propyl (17), N-benzyl (18) and N-arylmethyl derivatives (19-22) were subjected to ring closure reactions with phenylphosphonic dichloride in order to synthetize P-epimeric oxazaphosphorinanes 23a, 24-29 in which the hetero ring is condensed to ring D of the sterane skeleton. The stereostructures of the products were evaluated by 1H, 13C and 31P NMR spectroscopy. The geometry was optimized by utilizing the B3LYP DFT method. The NMR spectral data and the results of the ab initio calculations demonstrated that the stereostructure of the hetero ring was strongly affected by the rigid sterane framework condensed to it, and the phosphoramidate ring proved to adopt predominantly a distorted-boat conformation, regardless of the P-configuration. 相似文献
200.
Delfini M Di Cocco ME Piccioni F Porcelli F Borioni A Rodomonte A Del Giudice MR 《Bioorganic chemistry》2007,35(3):243-257
Two acetylcholinesterase (AChE) inhibitors structurally related to Tacrine, 6-methoxytacrine (1a) and 9-heptylamino-6-methoxytacrine (1b), and their interaction with Electrophorus Electricus AChE were investigated. The complete assignment of the 1H and 13C NMR spectra of 1a and 1b was performed by mono-dimensional and homo- and hetero-correlated two-dimensional NMR experiments. This study was undertaken to elucidate the interaction modes between AChE and 1a and 1b in solution, using NMR. The interaction between the two inhibitors and AChE was studied by the analysis of the motional parameters non-selective and selective spin-lattice relaxation times, thereby allowing the motional state of 1a and 1b, both free and bound with AChE, to be defined. The relaxation data pointed out the ligands molecular moiety most involved in the binding with AChE. The relevant ligand/enzyme interaction constants were also evaluated for both compounds and resulted to be 859 and 5412M(-1) for 1a and1b, respectively. 相似文献