全文获取类型
收费全文 | 1882篇 |
免费 | 79篇 |
国内免费 | 59篇 |
出版年
2023年 | 26篇 |
2022年 | 15篇 |
2021年 | 18篇 |
2020年 | 30篇 |
2019年 | 40篇 |
2018年 | 58篇 |
2017年 | 34篇 |
2016年 | 32篇 |
2015年 | 37篇 |
2014年 | 85篇 |
2013年 | 145篇 |
2012年 | 75篇 |
2011年 | 95篇 |
2010年 | 68篇 |
2009年 | 69篇 |
2008年 | 79篇 |
2007年 | 76篇 |
2006年 | 74篇 |
2005年 | 64篇 |
2004年 | 48篇 |
2003年 | 53篇 |
2002年 | 46篇 |
2001年 | 29篇 |
2000年 | 27篇 |
1999年 | 26篇 |
1998年 | 26篇 |
1997年 | 20篇 |
1996年 | 18篇 |
1995年 | 15篇 |
1994年 | 14篇 |
1993年 | 11篇 |
1992年 | 11篇 |
1991年 | 10篇 |
1990年 | 10篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1985年 | 35篇 |
1984年 | 50篇 |
1983年 | 24篇 |
1982年 | 39篇 |
1981年 | 59篇 |
1980年 | 39篇 |
1979年 | 40篇 |
1978年 | 37篇 |
1977年 | 37篇 |
1976年 | 33篇 |
1975年 | 40篇 |
1974年 | 37篇 |
1973年 | 35篇 |
1971年 | 6篇 |
排序方式: 共有2020条查询结果,搜索用时 31 毫秒
991.
Lignocellulosic biomass from agricultural crop residues and forest waste represents an abundant renewable resource for bioenergy and future biofuel. The current bottleneck of lignocellulosic biofuel production is the hydrolysis of biomass to sugar. To understand the enzymatic hydrolysis of complex biomasses, in this report, lignocellulolytic enzymes secretion by Phanerochaete chrysosporium cultivated in different natural lignocellulosic biomass such as corn stover, hay, sawdust, sugarcane baggase, wheat bran and wood chips were quantitatively analyzed with the iTRAQ technique using LC-MS/MS. A diverse groups of enzymes, including cellulases, glycoside hydrolases, hemicellulases, lignin degrading enzymes, peroxidases, esterases, lipases, chitinases, peptidases, protein translocating transporter and hypothetical proteins were quantified, of which several were novel lignocellulosic biomass hydrolyzing enzymes. The quantitative expression and regulation of lignocellulolytic enzymes by P. chrysosporium were dependent on the nature and complexity of lignocellulosic biomass as well as physical size of the biomass. The iTRAQ data revealed oxidative and hydrolytic lignin degrading mechanism of P. chrysosporium. Numerous proteins presumed to be involved in natural lignocellulosic biomass transformation and degradation were expressed and produced in variable quantities in response to different agricultural and forest wastes. 相似文献
992.
Novel chiral calix[4]arene derivatives bearing amino alcohol moieties at the lower rim have been synthesized from the reaction of p-tert-butylcalix[4]arene diester with various amino alcohols. The transport of amino acid esters (phenylglycine, phenylalanine, and tryptophan methyl esters hydrochloride) and mandelic acid were studied through chloroform bulk liquid membrane system using chiral calix[4]arenes 15-20. All these receptors have been found to act as carriers for transport of aromatic amino acid methylesters and mandelic acid from the aqueous source phase to the aqueous receiving phase. The influence of calixarene and guest structures upon transport through liquid membrane is discussed. 相似文献
993.
Arquimedes Paixão de Santana-FilhoGuilhermina Rodrigues Noleto Philip Albert James GorinLauro Mera de Souza Marcello IacominiGuilherme Lanzi Sassaki 《Carbohydrate polymers》2012,87(4):2730-2734
The most common method used to quantify lipopolysaccharide (LPS) in polysaccharide samples is the Limulus amebocyte lysate (LAL) test. It is a very sensitive and simple, although not accurate with samples containing carbohydrates, such as widely distributed (1 → 3)-linked β-glucans. Another method, the Polymyxin B assay, suffers interference with samples containing negatively charged polysaccharides. We have now developed a method to detect and quantify LPS in carbohydrate-containing samples, using GC-MS of derived acetylated 3-OH fatty acid methyl esters. The method proved to be robust, highly specific and sensitive, allowing detection of LPS at 1 ng, 100 times less than the amount of LPS frequently used as positive control in immunological experiments. In order to demonstrate the applicability of the method, 14 polysaccharide samples were analyzed. On two of them, the presence of LPS was detected at concentrations of 16.1 and 12.7 ng/300 μg polysaccharide. 相似文献
994.
The NMDA receptor (NMDAR) family of l-glutamate receptors are well known to have diverse roles in CNS function as well as in various neuropathological and psychiatric conditions. Until recently, the types of agents available to pharmacologically regulate NMDAR function have been quite limited in terms of mechanism of action and subtype selectivity. This has changed significantly in the past two years. The purpose of this review is to summarize the many drug classes now available for modulating NMDAR activity. Previously, this included competitive antagonists at the l-glutamate and glycine binding sites, high and low affinity channel blockers, and GluN2B-selective N-terminal domain binding site antagonists. More recently, we and others have identified new classes of NMDAR agents that are either positive or negative allosteric modulators (PAMs and NAMs, respectively). These compounds include the pan potentiator UBP646, the GluN2A-selective potentiator/GluN2C and GluN2D inhibitor UBP512, the GluN2D-selective potentiator UBP551, the GluN2C/GluN2D-selective potentiator CIQ as well as the new NMDAR-NAMs such as the pan-inhibitor UBP618, the GluN2C/GluN2D-selective inhibitor QZN46 and the GluN2A inhibitors UBP608 and TCN201. These new agents do not bind within the l-glutamate or glycine binding sites, the ion channel pore or the N-terminal regulatory domain. Collectively, these new allosteric modulators appear to be acting at multiple novel sites on the NMDAR complex. Importantly, these agents display improved subtype-selectivity and as NMDAR PAMs and NAMs, they represent a new generation of potential NMDAR therapeutics. 相似文献
995.
从假酸浆(Nicandra physaloides)全草中分离得到12个化合物,其中两个为新的醉茄内酯类化合物,经波谱学方法将其结构鉴定为nicandrenone methyl ether (1) 和26S-nicandrenone methyl ether (2);已知化合物为三个醉茄内酯,nicandrenone (3),Nic-7 (4),nicaphysalin E (5),以及pinosylvin monomethyl ether (6),2S-pinocembrin (7),(1S, 2R)-1, 2-bis (4-hydroxy-3-methoxyphenyl)-1, 3-propanediol (8),vanillin (9),indole-3-carboxylic acid (10),vanillic acid (11) 和drummondol (12)。 相似文献
996.
Yen1 is a nuclease identified in Saccharomyces cerevisiae that cleaves the Holliday junction (HJ) intermediate formed during homologous recombination. Alternative routes to disjoin HJs are performed by the Mus81/Mms4- and Sgs1/Top3/Rmi1-complexes. Here, we investigate the role of the Yen1 protein in the yeast Kluyveromyces lactis. We demonstrate that both yen1 mus81 and yen1 sgs1 double mutants displayed negative genetic interactions in the presence of DNA-damaging chemicals. To test if these phenotypes required the catalytic activity of Yen1, we introduced point mutations targeting the catalytic site of Yen1, which abolished the nuclease activity in vitro. Remarkably, catalytically inactive Yen1 did not exacerbate the hydroxyurea sensitivity of the sgs1Δ strain, which the yen1Δ allele did. In addition, overexpression of catalytically inactive Yen1 partially rescued the DNA damage sensitivity of both mus81 and sgs1 mutant strains albeit less efficiently than WT Yen1. These results suggest that Yen1 serves both a catalytic and non-catalytic role in its redundant function with Mus81 and Sgs1. Diploids lacking Mus81 had a severe defect in sporulation efficiency and crossover frequency, but diploids lacking both Mus81 and Yen1 showed no further reduction in spore formation. Hence, Yen1 had no evident role in meiosis. However, overexpression of WT Yen1, but not catalytically inactive Yen1 partially rescued the crossover defect in mus81/mus81 mutant diploids. Yen1 is a member of the RAD2/XPG-family of nucleases, but genetic analyses revealed no genetic interaction between yen1 and other family members (rad2, exo1 and rad27). In addition, yen1 mutants had normal nonhomologous end-joining efficiency. We discuss the similarities and differences between K. lactis Yen1 and Yen1/GEN1 from other organisms. 相似文献
997.
Shunsuke Imai Tatsuro Maruyama Masanori Osawa Motoyuki Hattori Ryuichiro Ishitani Osamu Nureki Ichio Shimada 《Biochimica et Biophysica Acta - Proteins and Proteomics》2012,1824(10):1129-1135
MgtE is a prokaryotic Mg2+ transporter that controls cellular Mg2+ concentrations. We previously reported crystal structures of the cytoplasmic region of MgtE, consisting of 2 domains, that is, N and CBS, in the Mg2+-free and Mg2+-bound forms. The Mg2+-binding sites lay at the interface of the 2 domains, making the Mg2+-bound form compact and globular. In the Mg2+-free structure, however, the domains are far apart, and the Mg2+-binding sites are destroyed. Therefore, it is unclear how Mg2+-free MgtE changes its conformation to accommodate Mg2+ ions. Here, we used paramagnetic relaxation enhancement (PRE) to characterize the relative orientation of the N and CBS domains in the absence of Mg2+ in solution. When the residues on the surface of the CBS domain were labeled with nitroxide tags, significant PRE effects were observed for the residues in the N domain. No single structure satisfied the PRE profiles, suggesting that the N and CBS domains are not fixed in a particular orientation in solution. We then conducted ensemble simulated annealing calculations in order to obtain the atomic probability density and visualize the spatial distribution of the N domain in solution. The results indicate that the N domain tends to occupy the space near its position in the Mg2+-bound crystal structure, facilitating efficient capture of Mg2+ with increased intracellular Mg2+ concentration, which is necessary to close the gate. 相似文献
998.
Jasmonic acid (JA) is a natural hormone regulator involved in development,responses against wounding and pathogen attack.Upon perception of pathogens,JA is synthesized and mediates a signaling cascade ... 相似文献
999.
This study examined the cytoprotective mechanisms of a combination of ischemic preconditioning (IPC) and allopurinol against liver injury caused by ischemia/reperfusion (I/R). Allopurinol (50 mg/kg) was intraperitoneally administered 18 and 1 h before sustained ischemia. A rat liver was preconditioned by 10 min of ischemia, followed by 10 min of reperfusion, and then subjected to 90 min of ischemia, followed by 5 h of reperfusion. Rats were pretreated with adenosine deaminase (ADA), 3,7-dimethyl-1-[2-propargyl]-xanthine (DMPX), and N-nitro-l-arginine methyl ester (l-NAME) before IPC. Hepatic nitrite and nitrate and eNOS protein expression levels were increased by the combination of IPC and allopurinol. This increase was attenuated by ADA, DMPX, and l-NAME. I/R induced an increase in alanine aminotransferase activity, whereas it decreased the hepatic glutathione level. A combination of IPC and allopurinol attenuated these changes, which were abolished by ADA, DMPX, and l-NAME. The increase in the liver wet weight-to-dry weight ratio after I/R was attenuated by the combination of IPC and allopurinol. In contrast, hepatic bile flow was decreased after I/R, which was attenuated by the combination of IPC and allopurinol. These changes were restored by l-NAME. I/R induced a decrease in the level of mitochondrial dehydrogenase, whereas it increased mitochondrial swelling. A combination of IPC and allopurinol attenuated these changes, which were restored by ADA, DMPX, and l-NAME. Our findings suggest that a combination of IPC and allopurinol reduces post-ischemic hepatic injury by enhancing NO generation. 相似文献
1000.
D. Segerbäck C.J. Calleman L. Ehrenberg G. Löfroth S. Osterman-Golkar 《Mutation research》1978,49(1):71-82
The present study explores the possibilities of using specific amino acids in haemoglobin for tissue dosimetry of alkylating agents. The well-known directly alkylating compound methyl methanesulfonate has been used as a model compound.In one experiment 3H-labelled methyl methanesulfonate was given to mice intraperitoneally at three dose levels. The degree of alkylation of haemoglobin exhibited a linear dependence on the quantity of methyl methanesulfonate injected. The degree of alkylation of guanine-N-7 in DNA indicated a slight positive deviation from linearity at high doses.After a single injection the degree of alkylation of cysteine-S and histidine-N-3 in haemoglobin decreased linearly with time reaching the value zero after about 40 days (the life-time of the erythrocytes in the mouse). This demonstrates a stability of these alkylated products, which is fundamental to their use as integral dose monitors.In a second experiment mice were treated with methyl methanesulfonate once a week over a period of 8 weeks. The experiment demonstrated an accumulation of alkylated groups in haemoglobin in agreement with expectation.A method for the quantitative determination of S-methylcysteine in a protein hydrolysate by gas chromatography was developed. 相似文献