全文获取类型
收费全文 | 370篇 |
免费 | 30篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 11篇 |
2020年 | 7篇 |
2019年 | 10篇 |
2018年 | 6篇 |
2017年 | 14篇 |
2016年 | 10篇 |
2015年 | 16篇 |
2014年 | 27篇 |
2013年 | 29篇 |
2012年 | 35篇 |
2011年 | 36篇 |
2010年 | 33篇 |
2009年 | 17篇 |
2008年 | 16篇 |
2007年 | 23篇 |
2006年 | 20篇 |
2005年 | 19篇 |
2004年 | 12篇 |
2003年 | 18篇 |
2002年 | 14篇 |
2001年 | 6篇 |
2000年 | 1篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 3篇 |
排序方式: 共有400条查询结果,搜索用时 31 毫秒
71.
Maike Lenz Niels Borlinghaus Leonie Weinmann Bettina M. Nestl 《World journal of microbiology & biotechnology》2017,33(11):199
Imine reductases are nicotinamide-dependent enzymes that catalyze the asymmetric reduction of various imines to the corresponding amine products. Owing to the increasing roles of chiral amines and heterocyclic compounds as intermediates for pharmaceuticals, the demand for novel selective synthesis strategies is vitally important. Recent studies have demonstrated the discovery and structural characterization of a number of stereoselective imine reductase enzymes. Here, we highlight recent progress in applying imine reductases for the formation of chiral amines and heterocycles. It particularly focuses on the utilization of imine reductases in reductive aminations of aldehydes and ketones with various amine nucleophiles, one of the most powerful reactions in the synthesis of chiral amines. Second, we report on the synthesis of saturated substituted N-heterocycles by combining them with further biocatalysts, such as carboxylic acid reductases, oxidases or transaminases. Finally, we summarize the latest applications of imine reductases in the promiscuous asymmetric hydrogenation of a highly reactive carbonyl compound and the engineering of the cofactor specificity from NADPH to NADH. 相似文献
72.
Maike Foraita Sophie Lehfeldt Klaus Reinhold Steven A. Ramm 《Journal of Insect Behavior》2017,30(2):170-179
Multiple mating by females is widespread and generates sperm competition among the ejaculates of rival males over fertilization. One way in which males can avoid or reduce sperm competition is by displacing or removing previous males’ sperm from female sperm stores. An apparent example of this occurs in the bushcricket Metaplastes ornatus. Males perform a specialised sperm removal behaviour (SRB), using their highly-derived subgenital plate, with which they remove sperm from the female’s spermatheca during the early phases of mating before transferring a spermatophore of their own. Here we investigated whether males strategically invest in SRB according to the amount of previously stored sperm present in females. Each male was tested twice, once with a female containing sperm (‘filled’ condition) and once with a female from whom most previously deposited sperm had recently been removed by another male (‘emptied’ condition). For comparison, a separate group of males was paired with virgin females. Males did not discriminate between non-virgin females in the ‘emptied’ or ‘filled’ conditions in terms of their investment in SRB, suggesting they may not able to perceive the amount of sperm present in the female’s spermatheca. By contrast, male investment in SRB was significantly reduced in pairings with virgin females, indicating that males are sensitive to some aspect of a female’s mating status. Our results thus suggest that males modulate SRB in response to female-mediated cues, possibly chemical cues left by previous males, which would not be present on virgin but would be on non-virgin females. 相似文献
73.
Frequent genes in rare diseases: panel‐based next generation sequencing to disclose causal mutations in hereditary neuropathies
下载免费PDF全文
![点击此处可从《Journal of neurochemistry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Maike F. Dohrn Nicola Glöckle Lejla Mulahasanovic Corina Heller Julia Mohr Christine Bauer Erik Riesch Andrea Becker Florian Battke Konstanze Hörtnagel Thorsten Hornemann Saranya Suriyanarayanan Markus Blankenburg Jörg B. Schulz Kristl G. Claeys Burkhard Gess Istvan Katona Andreas Ferbert Debora Vittore Alexander Grimm Stefan Wolking Ludger Schöls Holger Lerche G. Christoph Korenke Dirk Fischer Bertold Schrank Urania Kotzaeridou Gerhard Kurlemann Bianca Dräger Anja Schirmacher Peter Young Beate Schlotter‐Weigel Saskia Biskup 《Journal of neurochemistry》2017,143(5):507-522
74.
Katharina Nöbauer Karin Hummel Corina Mayrhofer Maike Ahrens Francis M.C. Setyabudi Markus Schmidt‐Heydt Martin Eisenacher Ebrahim Razzazi‐Fazeli 《Proteomics》2017,17(9)
Mass spectrometric identification of proteins in species lacking validated sequence information is a major problem in veterinary science. In the present study, we used ochratoxin A producing Penicillium verrucosum to identify and quantitatively analyze proteins of an organism with yet no protein information available. The work presented here aimed to provide a comprehensive protein identification of P. verrucosum using shotgun proteomics. We were able to identify 3631 proteins in an “ab initio” translated database from DNA sequences of P. verrucosum. Additionally, a sequential window acquisition of all theoretical fragment‐ion spectra analysis was done to find differentially regulated proteins at two different time points of the growth curve. We compared the proteins at the beginning (day 3) and at the end of the log phase (day 12). 相似文献
75.
Reconsidering environmental effects assessment of chemicals: Proposal for a dynamic testing strategy
Marion Junghans Maike Schaefer Wiebke Drost Enken Hassold Frauke Stock Matthias Dünne Tanja Juffernholz Wiebke Meyer Johannes Ranke 《Basic and Applied Ecology》2008,9(4):356-364
Certain substances may be hazardous to ecosystems. To be able to preserve the structures and functions of ecosystems, knowledge is required to qualify and quantify such hazards. To this end, biotests are indispensable tools. For the development and/or choice of biotests, special attention has to be drawn to conflicts between scientific demands and practical constraints. From a purely scientific point of view, experiments should be designed to maximise the ecological relevance of the obtained results. However, this often collides with the limited resources (budget, time, manpower) available. Furthermore, societal issues (e.g. animal welfare) have to be taken into account. Thus, it is necessary to develop a scientifically sound testing approach that avoids unnecessary animal testing, keeps the costs low, and can be performed within a short timeframe. The different perspectives of ecology, environmental toxicology, and environmental chemistry should be integrated into a balanced ecotoxicological approach. Accordingly, we propose a dynamic testing strategy, which is adapted to the substance (or substance group) in question and its mode(s) of action. 相似文献
76.
Cell cultures of Linum species store 6-methoxypodophyllotoxin (MPTOX), podophyllotoxin (PTOX) and related lignans as O-glucosides. UDP-glucose:(M)PTOX 7-O-glucosyltransferase has been detected and characterised in protein preparations of suspension-cultured cells of Linum nodiflorum L. (Linaceae). The maximal lignan glucoside contents in the cells are preceded by a rapid increase of the specific glucosyltransferase activity on day six of the culture period. MPTOX glucoside is the major lignan with up to 1.18 mg g(-1) of the cell dry wt which is more than 30-fold of the PTOX glucoside content. Of the three aryltetralin lignans tested as substrates, PTOX and MPTOX display comparable apparent K(m) values of 4.7 and 5.4 microM, respectively. 5'-Demethoxy-6-methoxypodophyllotoxin is converted with the highest velocity of 25.2 pkat mg(-1) while also possessing a higher K(m) of 14.7 microM. Two-substrate test series indicate that all three compounds compete for the active site of a single protein. The structurally similar lignan beta-peltatin acts as competitive inhibitor as well. However, the 6-O-glucosidation is most likely catalysed by a separate enzyme. The (M)PTOX 7-O-glucosyltransferase works best at a pH around 9 and a temperature around 35 degrees C. A 15-30% increase of the reaction rate is effected by the addition of 0.9 mM Mn(2+). 相似文献
77.
Bernhard Loll Maike Gebhardt Elmar Wahle Anton Meinhart 《Nucleic acids research》2009,37(21):7312-7320
EndoG is a ubiquitous nuclease that is translocated into the nucleus during apoptosis to participate in DNA degradation. The enzyme cleaves double- and single-stranded DNA and RNA. Related nucleases are found in eukaryotes and prokaryotes, which have evolved sophisticated mechanisms for genome protection against self-antagonizing nuclease activity. Common mechanisms of inhibition are secretion, sequestration into a separate cellular compartment or by binding to protein inhibitors. Although EndoG is silenced by compartmentalization into the mitochondrial intermembrane space, a nucleus-localized protein inhibitor protects cellular polynucleotides from degradation by stray EndoG under non-apoptotic conditions in Drosophila. Here, we report the first three-dimensional structure of EndoG in complex with its inhibitor EndoGI. Although the mechanism of inhibition is reminiscent of bacterial protein inhibitors, EndoGI has evolved independently from a generic protein-protein interaction module. EndoGI is a two-domain protein that binds the active sites of two monomers of EndoG, with EndoG being sandwiched between EndoGI. Since the amino acid sequences of eukaryotic EndoG homologues are highly conserved, this model is valid for eukaryotic dimeric EndoG in general. The structure indicates that the two active sites of EndoG occupy the most remote spatial position possible at the molecular surface and a concerted substrate processing is unlikely. 相似文献
78.
The final reactions of rosmarinic acid biosynthesis, the introduction of the aromatic 3- and 3′-hydroxyl groups, are catalysed
by cytochrome P450-dependent hydroxylases. The cDNAs encoding CYP98A14 as well as a NADPH:cytochrome P450 reductase (CPR)
were isolated from Coleus blumei and actively expressed in Saccharomyces cerevisiae. The CYP98A14-cDNA showed an open reading frame of 1521 nucleotides with high similarities to 4-coumaroylshikimate/quinate
3-hydroxylases. Yeast microsomes harbouring the CYP98A14 protein catalysed the 3-hydroxylation of 4-coumaroyl-3′,4′-dihydroxyphenyllactate
and the 3′-hydroxylation of caffeoyl-4′-hydroxyphenyllactate, in both cases forming rosmarinic acid. Apparent K
m-values for 4-coumaroyl-3′,4′-dihydroxyphenyllactate and caffeoyl-4′-hydroxyphenyllactate were determined to be at 5 μM and
40 μM, respectively. CYP98A14 differs from CYP98s from other plants, since 4-coumaroylshikimate or -quinate were not accepted
as substrates. Coexpression of the Coleus blumei CPR and CYP98A14 in the same yeast cells increased the hydroxylation activity up to sevenfold. CYP98A14 from Coleus blumei is a novel bifunctional cytochrome P450 specialised for rosmarinic acid biosynthesis. 相似文献
79.
Maike Kittelmann Johannes B. Schinko Marco Winkler Gregor Bucher Ernst A. Wimmer Nikola-Michael Prpic 《Development genes and evolution》2009,219(8):399-407
The genetic control of leg development is well characterized in the fly Drosophila melanogaster. These control mechanisms, however, must differ to some degree between different insect species to account for the morphological
diversity of thoracic legs in the insects. The legs of the flour beetle Tribolium castaneum differ from the Drosophila legs in their developmental mode as well as in their specific morphology especially at the larval stage. In order to identify
genes involved in the morphogenesis of the Tribolium larval legs, we have analyzed EGFP enhancer trap lines of Tribolium. We have identified the zfh2 gene as a novel factor required for normal leg development in Tribolium. RNA interference with zfh2 function leads to two alternative classes of leg phenotype. The loss of a leg segment boundary and the generation of ectopic
outgrowths in one class of phenotype suggest a role in leg segmentation and segment growth. The malformation of the pretarsal
claw in the second class of phenotype suggests a role in distal development and the morphogenesis of the claw-shaped morphology
of the pretarsus. This suggests that zfh2 is involved in the regulation of an unidentified target gene in a concentration-dependent manner. Our results demonstrate
that enhancer trap screens in T. castaneum have the potential to identify novel gene functions regulating specific developmental processes. 相似文献
80.
Haubold M Weise A Stephan H Dünker N 《International journal of biological sciences》2010,6(7):700-715
Bone morphogenetic proteins (BMPs) - expressed in the developing retina - are known to be involved in the regulation of cell proliferation and apoptosis in several tumor entities. The objective of this study was to determine the role of the BMP4 pathway in retinoblastoma cells, which are absent in a functional retinoblastoma (RB1) gene. BMP receptors were detected in all retinoblastoma cell lines investigated. A correct transmission of BMP signaling via the Smad1/5/8 pathway could be demonstrated in WERI-Rb1 retinoblastoma cells and application of recombinant human BMP4 resulted in an increase in apoptosis, which to a large extend is caspase independent. Cell proliferation was not affected by BMP4 signaling, although the pRb-related proteins p107 and p130, contributing to the regulation of the same genes, are still expressed. WERI-Rb1 cells exhibit elevated endogenous levels of p21(CIP1) and p53, but we did not detect any increase in p53, p21(CIP1)or p27(KIP1) expression levels. Id proteins became, however, strongly up-regulated upon exogenous BMP4 treatment. Thus, RB1 loss in WERI-Rb1 cells is obviously not compensated for by pRb-independent (e.g. p53-dependent) cell cycle control mechanisms, preventing an anti-proliferative response to BMP4, which normally induces cell cycle arrest. 相似文献