全文获取类型
收费全文 | 507篇 |
免费 | 16篇 |
学科分类
生物科学 | 523篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 6篇 |
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 11篇 |
2015年 | 20篇 |
2014年 | 27篇 |
2013年 | 22篇 |
2012年 | 44篇 |
2011年 | 35篇 |
2010年 | 14篇 |
2009年 | 22篇 |
2008年 | 30篇 |
2007年 | 28篇 |
2006年 | 24篇 |
2005年 | 24篇 |
2004年 | 22篇 |
2003年 | 17篇 |
2002年 | 15篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 14篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1981年 | 3篇 |
1978年 | 2篇 |
1973年 | 2篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有523条查询结果,搜索用时 15 毫秒
91.
Stephen P. East Clara Bantry White Oliver Barker Stephanie Barker James Bennett David Brown E. Andrew Boyd Christopher Brennan Chandana Chowdhury Ian Collins Emmanuelle Convers-Reignier Brian W. Dymock Rowena Fletcher David J. Haydon Mihaly Gardiner Stuart Hatcher Peter Ingram Paul Lancett Paul Mortenson Konstantinos Papadopoulos Lloyd G. Czaplewski 《Bioorganic & medicinal chemistry letters》2009,19(3):894-899
The synthesis and antibacterial activities of three chemotypes of DNA supercoiling inhibitors based on imidazolo[1,2-a]pyridine and [1,2,4]triazolo[1,5-a]pyridine scaffolds that target the ATPase subunits of DNA gyrase and topoisomerase IV (GyrB/ParE) is reported. The most potent scaffold was selected for optimization leading to a series with potent Gram-positive antibacterial activity and a low resistance frequency. 相似文献
92.
Peter R. Teske Colin L. McLay Jonathan Sandoval-Castillo Isabelle Papadopoulos Brent K. Newman Charles L. Griffiths Christopher D. McQuaid Nigel P. Barker Gaetan Borgonie Luciano B. Beheregaray 《Molecular phylogenetics and evolution》2009,53(1):23-33
Crabs of the family Hymenosomatidae are common in coastal and shelf regions throughout much of the southern hemisphere. One of the genera in the family, Hymenosoma, is represented in Africa and the South Pacific (Australia and New Zealand). This distribution can be explained either by vicariance (presence of the genus on the Gondwanan supercontinent and divergence following its break-up) or more recent transoceanic dispersal from one region to the other. We tested these hypotheses by reconstructing phylogenetic relationships among the seven presently-accepted species in the genus, as well as examining their placement among other hymenosomatid crabs, using sequence data from two nuclear markers (Adenine Nucleotide Transporter [ANT] exon 2 and 18S rDNA) and three mitochondrial markers (COI, 12S and 16S rDNA). The five southern African representatives of the genus were recovered as a monophyletic lineage, and another southern African species, Neorhynchoplax bovis, was identified as their sister taxon. The two species of Hymenosoma from the South Pacific neither clustered with their African congeners, nor with each other, and should therefore both be placed into different genera. Molecular dating supports a post-Gondwanan origin of the Hymenosomatidae. While long-distance dispersal cannot be ruled out to explain the presence of the family Hymenosomatidae on the former Gondwanan land-masses and beyond, the evolutionary history of the African species of Hymenosoma indicates that a third means of speciation may be important in this group: gradual along-coast dispersal from tropical towards temperate regions, with range expansions into formerly inhospitable habitat during warm climatic phases, followed by adaptation and speciation during subsequent cooler phases. 相似文献
93.
Annelise Chapalain Sylvie Chevalier Nicole Orange Laurence Murillo Vassilios Papadopoulos Marc G. J. Feuilloley 《PloS one》2009,4(6)
The translocator protein (TSPO), previously designated as peripheral-type benzodiazepine receptor, is a protein mainly located in the outer mitochondrial membrane of eukaryotic cells. TSPO is implicated in major physiological functions and functionally associated with other proteins such as the voltage-dependent anionic channel, also designated as mitochondrial porin. Surprisingly, a TSPO-related protein was identified in the photosynthetic bacterium Rhodobacter sphaeroides but it was initially considered as a relict of evolution. In the present study we cloned a tspO gene in Pseudomonas fluorescens MF37, a non-photosynthetic eubacterium and we used bioinformatics tools to identify TSPO in the genome of 97 other bacteria. P. fluorescens TSPO was recognized by antibodies against mouse protein and by PK 11195, an artificial ligand of mitochondrial TSPO. As in eukaryotes, bacterial TSPO appears functionally organized as a dimer and the apparent Kd for PK 11195 is in the same range than for its eukaryotic counterpart. When P. fluorescens MF37 was treated with PK 11195 (10−5 M) adhesion to living or artificial surfaces and biofilm formation activity were increased. Conversely, the apoptotic potential of bacteria on eukaryotic cells was significantly reduced. This effect of PK11195 was abolished in a mutant of P. fluorescens MF37 deficient for its major outer membrane porin, OprF. The present results demonstrate the existence of a bacterial TSPO that shares common structural and functional characteristics with its mammalian counterpart. This protein, apparently involved in adhesion and virulence, reveals the existence of a possible new inter kingdom signalling system and suggests that the human microbiome should be involuntarily exposed to the evolutionary pressure of benzodiazepines and related molecules. This discovery also represents a promising opportunity for the development of alternative antibacterial strategies. 相似文献
94.
Drosopoulou E Nestel D Nakou I Kounatidis I Papadopoulos NT Bourtzis K Mavragani-Tsipidou P 《Genetica》2011,139(6):723-732
The Ethiopian fruit fly, Dacus ciliatus, is an important pest of cucurbits, which recently invaded the Middle East. The genetics and cytogenetics of D. ciliatus have been scarcely studied. Such information is, however, an essential basis for understanding the biology of insect pests,
as well as for the design of modern control strategies. We report here the mitotic karyotype and detailed photographic maps
of the salivary gland polytene chromosomes of this species. The mitotic metaphase complement consists of six pairs of chromosomes,
including one pair of heteromorphic sex (XX/XY) chromosomes. The heterogametic sex is ascribed to the male. The analysis of
the salivary gland polytene complement shows a total number of five long chromosomes (10 polytene arms), which correspond
to the five autosomes of the mitotic nuclei, and a heterochromatic mass corresponding to the sex chromosomes. Banding patterns,
as well as the most characteristic features and prominent landmarks of each polytene chromosome are presented and discussed.
Chromosomal homologies between D. ciliatus and Bactrocera oleae are proposed by comparing chromosome banding patterns and by in situ hybridization of the hsp70 gene. 相似文献
95.
Papadopoulos C Arato K Lilienthal E Zerweck J Schutkowski M Chatain N Müller-Newen G Becker W de la Luna S 《The Journal of biological chemistry》2011,286(7):5494-5505
Dual specificity tyrosine phosphorylation-regulated kinases, DYRKs, are a family of conserved protein kinases that play key roles in the regulation of cell differentiation, proliferation, and survival. Of the five mammalian DYRKs, DYRK4 is the least studied family member. Here, we show that several splice variants of DYRK4 are expressed in tissue-specific patterns and that these variants have distinct functional capacities. One of these variants contains a nuclear localization signal in its extended N terminus that mediates its interaction with importin α3 and α5 and that is capable of targeting a heterologous protein to the nucleus. Consequently, the nucleocytoplasmic mobility of this variant differs from that of a shorter isoform in live cell imaging experiments. Other splicing events affect the catalytic domain, including a three-amino acid deletion within subdomain XI that markedly reduces the enzymatic activity of DYRK4. We also show that autophosphorylation of a tyrosine residue within the activation loop is necessary for full DYRK4 kinase activity, a defining feature of the DYRK family. Finally, by comparing the phosphorylation of an array of 720 peptides, we show that DYRK1A, DYRK2, and DYRK4 differ in their target recognition sequence and that preference for an arginine residue at position P -3 is a feature of DYRK1A but not of DYRK2 and DYRK4. Therefore, we highlight the use of subcellular localization as an important regulatory mechanism for DYRK proteins, and we propose that substrate specificity could be a source of functional diversity among DYRKs. 相似文献
96.
Panagiotis D. Kolokathis Evangelia Pantatosaki Christina-Anna Gatsiou Hervé Jobic George K. Papadopoulos 《Molecular simulation》2014,40(1-3):80-100
This study describes the development and application of a new computational methodology for calculating the self-diffusivity of sorbate molecules strongly confined within shape-selective nanoporous materials. An umbrella sampling strategy, employing repulsive walls to confine the sorbate within specific regions of the pore space, is invoked to extract free energy profiles with respect to the sorbate degrees of freedom. Based on these profiles, it is shown how the multidimensional problem of translational diffusion of benzene in flexible silicalite-1 can be reduced first to a six-dimensional problem, then to a three-dimensional (3D) problem and finally, to a 1D problem. A 3D free energy distribution is accumulated as a function of the benzene centre of mass position and ultimately reduced to a set of 1D profiles for the benzene centre of mass along the pore axes. From these profiles, the rate constants for jumps executed by benzene between sorption sites are calculated using transition state theory; from the latter rate constants, the low-occupancy self-diffusivity is obtained using the MESoRReD method [Kolokathis PD, Theodorou DN. On solving the master equation in spatially periodic systems. J Chem Phys. 2012;137:034112]. The activation energy for diffusion and preferred orientations in the various sorption states in silicalite are in very favourable agreement with available experimental measurements. 相似文献
97.
Ourania N. Kostopoulou Ekaterini C. Kouvela George E. Magoulas Thomas Garnelis Ioannis Panagoulias Maria Rodi Georgios Papadopoulos Athanasia Mouzaki George P. Dinos Dionissios Papaioannou Dimitrios L. Kalpaxis 《Nucleic acids research》2014,42(13):8621-8634
Chloramphenicol (CAM) is a broad-spectrum antibiotic, limited to occasional only use in developed countries because of its potential toxicity. To explore the influence of polyamines on the uptake and activity of CAM into cells, a series of polyamine–CAM conjugates were synthesized. Both polyamine architecture and the position of CAM-scaffold substitution were crucial in augmenting the antibacterial and anticancer potency of the synthesized conjugates. Compounds 4 and 5, prepared by replacement of dichloro-acetyl group of CAM with succinic acid attached to N4 and N1 positions of N8,N8-dibenzylspermidine, respectively, exhibited higher activity than CAM in inhibiting the puromycin reaction in a bacterial cell-free system. Kinetic and footprinting analysis revealed that whereas the CAM-scaffold preserved its role in competing with the binding of aminoacyl-tRNA 3′-terminus to ribosomal A-site, the polyamine-tail could interfere with the rotatory motion of aminoacyl-tRNA 3′-terminus toward the P-site. Compared to CAM, compounds 4 and 5 exhibited comparable or improved antibacterial activity, particularly against CAM-resistant strains. Compound 4 also possessed enhanced toxicity against human cancer cells, and lower toxicity against healthy human cells. Thus, the designed conjugates proved to be suitable tools in investigating the ribosomal catalytic center plasticity and some of them exhibited greater efficacy than CAM itself. 相似文献
98.
Ivan Mrkic Mohamed Abughren Jasna Nikolic Uros Andjelkovic Emilia Vassilopoulou Athanassios Sinaniotis Arnd Petersen Nikolaos G. Papadopoulos Marija Gavrovic-Jankulovic 《Molecular biotechnology》2014,56(6):498-506
Allergy to banana fruit appears to have become an important cause of fruit allergy in Europe. Among five allergens that have been found, beta-1,3-glucanase denoted as Mus a 5 was identified as a candidate allergen for the component-resolved allergy diagnosis of banana allergy. Because of the variations in protein levels in banana fruit, in this study Mus a 5 was produced as a fusion protein with glutathione-S-transferase in Escherichia coli. The recombinant Mus a 5 was purified under native conditions by a combination of affinity, ion-exchange, and reversed phase chromatography. N-terminal sequence was confirmed by Edman degradation and 55 % of the primary structure was identified by mass fingerprint, while the secondary structure was assessed by circular dichroism spectroscopy. IgG reactivity of recombinant protein was shown in 2-D immunoblot with anti-Mus a 5 antibodies, while IgG and IgE binding to natural Mus a 5 was inhibited with the recombinant Mus a 5 in immunoblot inhibition test. IgE reactivity of recombinant Mus a 5 was shown in ELISA within a group of ten persons sensitized to banana fruit. Recombinant Mus a 5 is a novel reagent suitable for the component-resolved allergy diagnosis of banana allergy. 相似文献
99.
100.
Theofilos Papadopoulos Rudolf Schemm Helmut Grubmüller Nils Brose 《The Journal of biological chemistry》2015,290(13):8256-8270
Signaling at nerve cell synapses is a key determinant of proper brain function, and synaptic defects—or synaptopathies—are at the basis of many neurological and psychiatric disorders. In key areas of the mammalian brain, such as the hippocampus or the basolateral amygdala, the clustering of the scaffolding protein Gephyrin and of γ-aminobutyric acid type A receptors at inhibitory neuronal synapses is critically dependent upon the brain-specific guanine nucleotide exchange factor Collybistin (Cb). Accordingly, it was discovered recently that an R290H missense mutation in the diffuse B-cell lymphoma homology domain of Cb, which carries the guanine nucleotide exchange factor activity, leads to epilepsy and intellectual disability in human patients. In the present study, we determined the mechanism by which the CbR290H mutation perturbs inhibitory synapse formation and causes brain dysfunction. Based on a combination of biochemical, cell biological, and molecular dynamics simulation approaches, we demonstrate that the R290H mutation alters the strength of intramolecular interactions between the diffuse B-cell lymphoma homology domain and the pleckstrin homology domain of Cb. This defect reduces the phosphatidylinositol 3-phosphate binding affinity of Cb, which limits its normal synaptogenic activity. Our data indicate that impairment of the membrane lipid binding activity of Cb and a consequent defect in inhibitory synapse maturation represent a likely molecular pathomechanism of epilepsy and mental retardation in humans. 相似文献