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51.
Marine cyanobacteria are a rich source of complex bioactive secondary metabolites which derive from mixed biosynthetic pathways. Recently, several marine cyanobacterial natural products have garnered much attention due to their intriguing structures and exciting anti-proliferative or cancer cell toxic activities. Several other recently discovered secondary metabolites exhibit insightful neurotoxic activities whereas others are showing pronounced anti-inflammatory activity. A number of anti-infective compounds displaying activity against neglected diseases have also been identified, which include viridamides A and B, gallinamide A, dragonamide E, and the almiramides. 相似文献
52.
53.
Gehret JJ Gu L Gerwick WH Wipf P Sherman DH Smith JL 《The Journal of biological chemistry》2011,286(16):14445-14454
Curacin A is a polyketide synthase (PKS)-non-ribosomal peptide synthetase-derived natural product with potent anticancer properties generated by the marine cyanobacterium Lyngbya majuscula. Type I modular PKS assembly lines typically employ a thioesterase (TE) domain to off-load carboxylic acid or macrolactone products from an adjacent acyl carrier protein (ACP) domain. In a striking departure from this scheme the curacin A PKS employs tandem sulfotransferase and TE domains to form a terminal alkene moiety. Sulfotransferase sulfonation of β-hydroxy-acyl-ACP is followed by TE hydrolysis, decarboxylation, and sulfate elimination (Gu, L., Wang, B., Kulkarni, A., Gehret, J. J., Lloyd, K. R., Gerwick, L., Gerwick, W. H., Wipf, P., Håkansson, K., Smith, J. L., and Sherman, D. H. (2009) J. Am. Chem. Soc. 131, 16033–16035). With low sequence identity to other PKS TEs (<15%), the curacin TE represents a new thioesterase subfamily. The 1.7-Å curacin TE crystal structure reveals how the familiar α/β-hydrolase architecture is adapted to specificity for β-sulfated substrates. A Ser-His-Glu catalytic triad is centered in an open active site cleft between the core domain and a lid subdomain. Unlike TEs from other PKSs, the lid is fixed in an open conformation on one side by dimer contacts of a protruding helix and on the other side by an arginine anchor from the lid into the core. Adjacent to the catalytic triad, another arginine residue is positioned to recognize the substrate β-sulfate group. The essential features of the curacin TE are conserved in sequences of five other putative bacterial ACP-ST-TE tridomains. Formation of a sulfate leaving group as a biosynthetic strategy to facilitate acyl chain decarboxylation is of potential value as a route to hydrocarbon biofuels. 相似文献
54.
The structural assignment of new natural product molecules supports research in a multitude of disciplines that may lead to new therapeutic agents and or new understanding of disease biology. However, reports of numerous structural revisions, even of recently elucidated natural products, inspired the present survey of techniques used in structural misassignments and subsequent revisions in the context of constitutional or configurational errors. Given the comparatively recent development of marine natural products chemistry, coincident with modern spectroscopy, it is of interest to consider the relative roles of spectroscopy and chemical synthesis in the structure elucidation and revision of those marine natural products that were initially misassigned. Thus, a tabulated review of all marine natural product structural revisions from 2005 to 2010 is organized according to structural motif revised. Misassignments of constitution are more frequent than perhaps anticipated by reliance on HMBC and other advanced NMR experiments, especially when considering the full complement of all natural products. However, these techniques also feature prominently in structural revisions, specifically of marine natural products. Nevertheless, as is the case for revision of relative and absolute configuration, total synthesis is a proven partner for marine, as well as terrestrial, natural products structure elucidation. It also becomes apparent that considerable 'detective work' remains in structure elucidation, in spite of the spectacular advances in spectroscopic techniques. 相似文献
55.
Characterization of Cyanobacterial Hydrocarbon Composition and Distribution of Biosynthetic Pathways
R. Cameron Coates Sheila Podell Anton Korobeynikov Alla Lapidus Pavel Pevzner David H. Sherman Eric E. Allen Lena Gerwick William H. Gerwick 《PloS one》2014,9(1)
Cyanobacteria possess the unique capacity to naturally produce hydrocarbons from fatty acids. Hydrocarbon compositions of thirty-two strains of cyanobacteria were characterized to reveal novel structural features and insights into hydrocarbon biosynthesis in cyanobacteria. This investigation revealed new double bond (2- and 3-heptadecene) and methyl group positions (3-, 4- and 5-methylheptadecane) for a variety of strains. Additionally, results from this study and literature reports indicate that hydrocarbon production is a universal phenomenon in cyanobacteria. All cyanobacteria possess the capacity to produce hydrocarbons from fatty acids yet not all accomplish this through the same metabolic pathway. One pathway comprises a two-step conversion of fatty acids first to fatty aldehydes and then alkanes that involves a fatty acyl ACP reductase (FAAR) and aldehyde deformylating oxygenase (ADO). The second involves a polyketide synthase (PKS) pathway that first elongates the acyl chain followed by decarboxylation to produce a terminal alkene (olefin synthase, OLS). Sixty-one strains possessing the FAAR/ADO pathway and twelve strains possessing the OLS pathway were newly identified through bioinformatic analyses. Strains possessing the OLS pathway formed a cohesive phylogenetic clade with the exception of three Moorea strains and Leptolyngbya sp. PCC 6406 which may have acquired the OLS pathway via horizontal gene transfer. Hydrocarbon pathways were identified in one-hundred-forty-two strains of cyanobacteria over a broad phylogenetic range and there were no instances where both the FAAR/ADO and the OLS pathways were found together in the same genome, suggesting an unknown selective pressure maintains one or the other pathway, but not both. 相似文献
56.
Peter Sörös Faisal Al-Otaibi Savio WH Wong J Kevin Shoemaker Seyed M Mirsattari Vladimir Hachinski Ruth E Martin 《BMC neurology》2011,11(1):20
Background
Various functional resonance imaging, magnetoencephalographic and lesion studies suggest the involvement of the insular cortex in the control of swallowing. However, the exact location of insular activation during swallowing and its functional significance remain unclear. 相似文献57.
Han B Gross H McPhail KL Goeger D Maier CS Gerwick WH 《Journal of microbiology and biotechnology》2011,21(9):930-936
Two new cyclic depsipeptides wewakamide A (1) and guineamide G (2) have been isolated from the marine cyanobacterium Lyngbya semiplena and Lyngbya majuscula, respectively, collected from Papua New Guinea. The amino and hydroxy acid partial structures of wewakamide A and guineamide G were elucidated through extensive spectroscopic techniques, including HR-FABMS, 1D (1)H and (13)C NMR, as well as 2D COSY, HSQC, HSQCTOCSY, and HMBC spectra. The sequence of the residues of wewakamide A was determined through a combination of ESI-MS/MS, HMBC, and ROESY. Wewakamide A possesses a β-amino acid, 3-amino-2-methylbutanoic acid (Maba) residue, which has only been previously identified in two natural products, guineamide B (3) and dolastatin D (4). Although both new compounds (1,2) showed potent brine shrimp toxicity, only guineamide G displayed significant cytotoxicity to a mouse neuroblastoma cell line with LC(50) values of 2.7 micrometer. 相似文献
58.
Charusanti P Fong NL Nagarajan H Pereira AR Li HJ Abate EA Su Y Gerwick WH Palsson BO 《PloS one》2012,7(3):e33727
Adaptation is normally viewed as the enemy of the antibiotic discovery and development process because adaptation among pathogens to antibiotic exposure leads to resistance. We present a method here that, in contrast, exploits the power of adaptation among antibiotic producers to accelerate the discovery of antibiotics. A competition-based adaptive laboratory evolution scheme is presented whereby an antibiotic-producing microorganism is competed against a target pathogen and serially passed over time until the producer evolves the ability to synthesize a chemical entity that inhibits growth of the pathogen. When multiple Streptomyces clavuligerus replicates were adaptively evolved against methicillin-resistant Staphylococcus aureus N315 in this manner, a strain emerged that acquired the ability to constitutively produce holomycin. In contrast, no holomycin could be detected from the unevolved wild-type strain. Moreover, genome re-sequencing revealed that the evolved strain had lost pSCL4, a large 1.8 Mbp plasmid, and acquired several single nucleotide polymorphisms in genes that have been shown to affect secondary metabolite biosynthesis. These results demonstrate that competition-based adaptive laboratory evolution can constitute a platform to create mutants that overproduce known antibiotics and possibly to discover new compounds as well. 相似文献
59.
D Montoya C Arévalo S Gonzales F Aristizabal WH Schwarz 《Journal of industrial microbiology & biotechnology》2001,27(5):329-335
Thirteen new Clostridium strains, previously isolated from soil and found to produce high amounts of solvents from glucose, hydrolyzed a great variety
of α- and β-glycans, including raw starch, xylan, pectin, inulin and cellulose. The sequences of the PCR-amplified DNA fragments
containing the variable 3′ part of one of the 16S rRNA genes were 99.5% identical. The macrorestriction pattern of two endonucleolytic
digests of chromosomal DNA in the pulsed-field gel electrophoresis (PFGE) confirmed their high homogeneity on the DNA level.
The complete 16S rRNA gene sequence of three selected strains was 99.8% identical to the 16S rRNA gene sequence from Clostridium butyricum and separates them from C. acetobutylicum. To the closely related four species of solventogenic clostridia a new group of strains has to be added, which has a great
potential for the direct fermentation of biomass.
Journal of Industrial Microbiology & Biotechnology (2001) 27, 329–335.
Received 12 September 2000/ Accepted in revised form 25 July 2001 相似文献
60.
Gerwick L Demers NE Bayne CJ 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》1999,124(3):329-334
Sympathetic activation leading to increased levels of blood catecholamines, and stimulation of the hypothalamic-pituitary inter-renal axis leading to increased cortisol, are difficult to avoid when handling animals. Yet, in research on effects of acute stress, elicitation of such responses must be minimized in the control groups. The work examines means to achieve a minimally disturbed state in rainbow trout (Oncorhynchus mykiss). Level of arousal was determined by adrenaline and cortisol concentrations in plasma, and by the spleen:somatic index. Fish were prepared for bleeding by rapid capture and concussion, by infusion of anesthetic into the undisturbed home tank, by confinement in black boxes, or by being fed alpha- and beta-receptor antagonists. Even when done quickly, netting and concussion yielded fish with ca. 200-pmol adrenaline/ml plasma. Cortisol was elevated (to > 10 ng/ml) within 30 s of stress initiation. Surreptitious infusion of anesthetic (2-phenoxyethanol, PE) into tanks yielded fish with lower adrenaline levels (means 19.34 and 19.58 pmols/ml in home tank and black boxes, respectively). Among fish given phentolamine and propranolol, spleen:somatic indices and plasma adrenaline were higher than in diet controls, whether undisturbed or stressed, indicative of successful receptor blockade. Since careful infusion of 2-PE yielded the lowest adrenaline levels, and requires no special apparatus, it is the method of choice for obtaining minimally stressed fish. 相似文献