全文获取类型
收费全文 | 560篇 |
免费 | 41篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 8篇 |
2021年 | 12篇 |
2020年 | 4篇 |
2019年 | 5篇 |
2018年 | 10篇 |
2017年 | 12篇 |
2016年 | 18篇 |
2015年 | 25篇 |
2014年 | 24篇 |
2013年 | 25篇 |
2012年 | 52篇 |
2011年 | 54篇 |
2010年 | 34篇 |
2009年 | 27篇 |
2008年 | 46篇 |
2007年 | 42篇 |
2006年 | 41篇 |
2005年 | 41篇 |
2004年 | 33篇 |
2003年 | 21篇 |
2002年 | 19篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1987年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1971年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有601条查询结果,搜索用时 78 毫秒
441.
Ashima Saxena James M Fedorko C R Vinayaka Rohit Medhekar Zoran Radi? Palmer Taylor Oksana Lockridge Bhupendra P Doctor 《European journal of biochemistry》2003,270(22):4447-4458
E2020 (R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methyl)piperidine hydrochloride is a piperidine-based acetylcholinesterase (AChE) inhibitor that was approved for the treatment of Alzheimer's disease in the United States. Structure-activity studies of this class of inhibitors have indicated that both the benzoyl containing functionality and the N-benzylpiperidine moiety are the key features for binding and inhibition of AChE. In the present study, the interaction of E2020 with cholinesterases (ChEs) with known sequence differences, was examined in more detail by measuring the inhibition constants with Torpedo AChE, fetal bovine serum AChE, human butyrylcholinesterase (BChE), and equine BChE. The basis for particular residues conferring selectivity was then confirmed by using site-specific mutants of the implicated residue in two template enzymes. Differences in the reactivity of E2020 toward AChE and BChE (200- to 400-fold) show that residues at the peripheral anionic site such as Asp74(72), Tyr72(70), Tyr124(121), and Trp286(279) in mammalian AChE may be important in the binding of E2020 to AChE. Site-directed mutagenesis studies using mouse AChE showed that these residues contribute to the stabilization energy for the AChE-E2020 complex. However, replacement of Ala277(Trp279) with Trp in human BChE does not affect the binding of E2020 to BChE. Molecular modeling studies suggest that E2020 interacts with the active-site and the peripheral anionic site in AChE, but in the case of BChE, as the gorge is larger, E2020 cannot simultaneously interact at both sites. The observation that the KI value for mutant AChE in which Ala replaced Trp286 is similar to that for wild-type BChE, further confirms our hypothesis. 相似文献
442.
443.
Ristic Z Momcilović I Fu J Callegari E DeRidder BP 《Journal of plant physiology》2007,164(12):1564-1571
Chloroplast protein synthesis elongation factor, EF-Tu, has been implicated in heat tolerance in maize. The recombinant precursor of this protein, pre-EF-Tu, has been found to exhibit chaperone activity and protect heat-labile proteins, such as citrate synthase and malate dehydrogenase, from thermal aggregation. Chloroplast EF-Tu is highly conserved and it is possible that the chaperone activity of this protein is not species-specific. In this study, we investigated the effect of native wheat pre-EF-Tu on thermal aggregation of rubisco activase. Additionally, we investigated the effect of native and recombinant maize pre-EF-Tu on activase aggregation. Activase was chosen because it displays an exceptional sensitivity to thermal aggregation and constrains photosynthesis at high temperature. The native precursors of both wheat and maize EF-Tu displayed chaperone activity, as shown by the capacity of both proteins to reduce thermal aggregation of rubisco activase in vitro. Similarly, the recombinant maize pre-EF-Tu protected activase from thermal aggregation. This is the first report on chaperone activity of native pre-EF-Tu and the first evidence for thermal protection of a photosynthetic enzyme by this putative chaperone. The results are consistent with the hypothesis that chloroplast EF-Tu plays a functional role in heat tolerance by acting as a molecular chaperone. 相似文献
444.
Two portable instruments, designed to evaluate epidermal UV screening in leaves, were compared: the Dualex and the UV-A-PAM
fluorimeter. Both instruments excite chlorophyll fluorescence at the same UV wavelengths but reference excitation is in the
red and the blue spectral range in the former and the latter fluorimeter, respectively. When analyzing green leaves, general
agreement of the data is obtained with the two instruments. In the presence of anthocyanins, the UV-A-PAM fluorimeter provided
higher estimates for epidermal UV transmittance than the Dualex fluorimeter, which was attributed to absorption of blue excitation
light by anthocyanins. By comparing data from the instruments, anthocyanin-dependent transmittance of 50% was determined in
abaxial sides of some autumn leaves, and also in abaxial sides of tropical shade plants. Further, with leaves of chlorophyll
b-less mutants of H. vulgare, unusually high epidermal UV transmittance was detected but this was attributed to the lack of chlorophyll b absorption and, in addition, to absorption of blue radiation by xanthophylls which are not functionally connected to photosystems. 相似文献
445.
Margetić P Miklić D Rakić-Ersek V Doko Z Lubina ZI Brkljacić B 《Collegium antropologicum》2007,31(1):279-284
The purpose of the study was to assess the value of ultrasonography in the diagnosis of Achilles tendon rupture, by comparing initial ultrasonographic scans and direct intraoperative findings, as well as to follow up the healing process in operatively and conservatively treated patients. Ultrasound examination was performed in 100 patients (91 males and 9 females, with mean age of 46 years) with clinically suspicious Achilles tendon ruptures. Ultrasonographic findings were compared with intraoperative findings. Eighty-eight patients underwent surgery and twelve patients were treated conservatively. Complete ruptures were diagnosed by ultrasound in 88 patients, and partial ruptures in 12 patients. The length of the tendon (Pearson r = 0.973, p < 0.001, Spearman p = 0.972, p < 0.001) and the size of the rupture (Pearson r = 0.940, p < 0.001, Spearman p = 0.905, p < 0.001) measured before surgery by ultrasound and directly during surgery showed a high correlation. Out of 88 operatively treated patients, 86 had a complete rupture and two had a partial rupture. All patients were examined 3, 5, 8, and 12 weeks after injury or after surgery. In the first five weeks, there were statistically significant differences noted between these two groups. Operatively treated tendons healed more quickly, but after eight and twelve weeks this difference had disappeared. Our study showed that ultrasound is an excellent imaging method for confirming the clinical diagnosis of Achilles tendon rupture as well as for following up the process of tendon healing. 相似文献
446.
This study examined the relationship between coping strategies, anxiety and depression levels and burn injury characteristics in the early phase of the treatment in burn-injured patients. Seventy patients with severe burns were interviewed within two weeks of their burn trauma. Coping strategies were measured by the coping with burns questionnaire (CBQ). Anxiety and depression levels were assessed with the Beck Depression Inventory and the Beck Anxiety Inventory. There were no statistically significant gender differences in various coping strategies. Avoidance was associated with higher levels of anxiety, depression and hopelessness. The percentage of total body surface area (TBSA) and localization of burns were not associated with coping patterns. Implications for the assessment and management of burn injured patients were discussed. 相似文献
447.
Matthias Westhues Tobias A. Schrag Claas Heuer Georg Thaller H. Friedrich Utz Wolfgang Schipprack Alexander Thiemann Felix Seifert Anita Ehret Armin Schlereth Mark Stitt Zoran Nikoloski Lothar Willmitzer Chris C. Schön Stefan Scholten Albrecht E. Melchinger 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2017,130(9):1927-1939
448.
Willian E. Amaral de Lima Ander Francisco Elaine F.F. da Cunha Zoran Radic Palmer Taylor 《Journal of biomolecular structure & dynamics》2017,35(6):1272-1282
Butyryl cholinesterase (BChE) has been seen as a key enzyme in the search for new strategies in the treatment of poisoning by organophosphates (OPs), since human BChE (HssBChE), complexed with the appropriate oxime, can be a suitable scavenger and deactivator for OPs in the blood stream. However, the efficacy of HssBChE is limited by its strict stoichiometric scavenging, slow reactivation, and propensity for aging. The improvement of the reactivation rate by new and more efficient oximes could contribute to mitigate this problem and increase the HssBChE efficiency as scavenger. Several oximes have been synthesized and tested with this goal, some with promising results, but the mechanistic aspects of the reactivation reaction are not fully understood yet. In order to better investigate this mechanism, docking and mixed quantum and molecular mechanics combined with principal components analysis were performed here to evaluate the capacity of reactivation and determine the preferred route for the reactivation reaction of two new oximes on HssBChE inhibited by the neurotoxic agents cyclosarin and sarin. Plots of potential energies were calculated and all the transition states of the reactional mechanism were determined. Our results showed a good correlation with experimental data and pointed to the most efficient oxime with both OPs. The protocol used could be a suitable tool for a preliminary evaluation of the HssBChE reactivation rates by new oximes. 相似文献
449.
450.
Blackleg fungi [Leptosphaeria maculans (asexual stage Phoma lingam) and Leptosphaeria biglobosa] are devastating plant pathogens with well-established stratagems to invade crucifers, including the production of enzymes that detoxify plant defenses such as phytoalexins. The significant roles of brassinin, both as a potent crucifer phytoalexin and a biosynthetic precursor of several other plant defenses, make it critical to plant fitness. Brassinin oxidase, a detoxifying enzyme produced by L. maculans both in vitro and in planta, catalyzes the detoxification of brassinin by the unusual oxidative transformation of a dithiocarbamate to an aldehyde. Purified brassinin oxidase has an apparent molecular mass of 57 kDa, is approximately 20% glycosylated, and accepts a wide range of cofactors, including quinones and flavins. Purified brassinin oxidase was used to screen a library of brassinin analogues and crucifer phytoalexins for potential inhibitory activity. Unexpectedly, it was determined that the crucifer phytoalexins camalexin and cyclobrassinin are competitive inhibitors of brassinin oxidase. This discovery suggests that camalexin could protect crucifers from attacks by L. maculans because camalexin is not metabolized by this pathogen and is a strong mycelial growth inhibitor. 相似文献