全文获取类型
收费全文 | 873篇 |
免费 | 63篇 |
出版年
2023年 | 7篇 |
2022年 | 17篇 |
2021年 | 30篇 |
2020年 | 15篇 |
2019年 | 28篇 |
2018年 | 29篇 |
2017年 | 27篇 |
2016年 | 35篇 |
2015年 | 59篇 |
2014年 | 64篇 |
2013年 | 61篇 |
2012年 | 96篇 |
2011年 | 67篇 |
2010年 | 56篇 |
2009年 | 25篇 |
2008年 | 46篇 |
2007年 | 40篇 |
2006年 | 40篇 |
2005年 | 29篇 |
2004年 | 27篇 |
2003年 | 29篇 |
2002年 | 20篇 |
2001年 | 3篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1980年 | 6篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1976年 | 1篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1957年 | 1篇 |
1953年 | 1篇 |
排序方式: 共有936条查询结果,搜索用时 15 毫秒
151.
Dalia Rokhsana Tao A. G. Large Morgan C. Dienst Marius Retegan Frank Neese 《Journal of biological inorganic chemistry》2016,21(4):491-499
CO dehydrogenase (CODH) is an environmentally crucial bacterial enzyme that oxidizes CO to CO2 at a Mo–Cu active site. Despite the close to atomic resolution structure (1.1 Å), significant uncertainties have remained with regard to the protonation state of the water-derived equatorial ligand coordinated at the Mo-center, as well as the nature of intermediates formed during the catalytic cycle. To address the protonation state of the equatorial ligand, we have developed a realistic in silico QM model (~179 atoms) containing structurally essential residues surrounding the active site. Using our QM model, we examined each plausible combination of redox states (MoVI–CuI, MoV–CuII, MoV–CuI, and MoIV–CuI) and Mo-coordinated equatorial ligands (O2?, OH?, H2O), as well as the effects of second-sphere residues surrounding the active site. Herein, we present a refined computational model for the Mo(VI) state in which Glu763 acts as an active site base, leading to a MoO2-like core and a protonated Glu763. Calculated structural and spectroscopic data (hyperfine couplings) are in support of a MoO2-like core in agreement with XRD data. The calculated two-electron reduction potential (E = ?467 mV vs. SHE) is in reasonable agreement with the experimental value (E = ?558 mV vs. SHE) for the redox couple comprising an equatorial oxo ligand and protonated Glu763 in the MoVI–CuI state and an equatorial water in the MoIV–CuI state. We also suggest a potential role of second-sphere residues (e.g., Glu763, Phe390) based on geometric changes observed upon exclusion of these residues in the most plausible oxidized states. 相似文献
152.
153.
Phycobiliproteins and phytochromes are light-harvesting and light-sensing proteins containing linear tetrapyrroles, so-called bile chromophores. The chromophores in certain biliproteins, including the phytochromes, isomerize reversibly from a stable Z-configuration to a stable E-configuration when irradiated with light of the appropriate wavelength. Here, we report the crystal structure of alpha-phycoerythrocyanin with its chromophore in the E-configuration, compare it with the Z-configuration found in trimeric phycoerythrocyanin, and reveal the structural bases of the isomerization. The geometric changes of the chromophore account for the large spectral shift, which characterizes the overall transition. Interactions of the chromophore A and D pyrrole rings with flexible protein moieties are required for the formation and stabilization of the isomers. We predict that the results will hold for all photoactive biliproteins. 相似文献
154.
Daniella Schatz Guy Schleyer Marius R. Saltvedt Ruth-Anne Sandaa Ester Feldmesser Assaf Vardi 《The ISME journal》2021,15(12):3714
Extracellular vesicles are produced by organisms from all kingdoms and serve a myriad of functions, many of which involve cell-cell signaling, especially during stress conditions and host-pathogen interactions. In the marine environment, communication between microorganisms can shape trophic level interactions and population succession, yet we know very little about the involvement of vesicles in these processes. In a previous study, we showed that vesicles produced during viral infection by the ecologically important model alga Emiliania huxleyi, could act as a pro-viral signal, by expediting infection and enhancing the half-life of the virus in the extracellular milieu. Here, we expand our laboratory findings and show the effect of vesicles on natural populations of E. huxleyi in a mesocosm setting. We profile the small-RNA (sRNA) cargo of vesicles that were produced by E. huxleyi during bloom succession, and show that vesicles applied to natural assemblages expedite viral infection and prolong the half-life of this major mortality agent of E. huxleyi. We subsequently reveal that exposure of the natural assemblage to E. huxleyi-derived vesicles modulates not only host-virus dynamics, but also other components of the microbial food webs, thus emphasizing the importance of extracellular vesicles to microbial interactions in the marine environment.Subject terms: Virus-host interactions, Microbial ecology, Water microbiology 相似文献
155.
Genetic differentiation between divergent populations is often greater in chromosome centres than peripheries. Commonly overlooked, this broadscale differentiation pattern is sometimes ascribed to heterogeneity in crossover rate and hence linked selection within chromosomes, but the underlying mechanisms remain incompletely understood. A literature survey across 46 organisms reveals that most eukaryotes indeed exhibit a reduced crossover rate in chromosome centres relative to the peripheries. Using simulations of populations diverging into ecologically different habitats through sorting of standing genetic variation, we demonstrate that such chromosome‐scale heterogeneity in crossover rate, combined with polygenic divergent selection, causes stronger hitchhiking and especially barriers to gene flow across chromosome centres. Without requiring selection on new mutations, this rapidly leads to elevated population differentiation in the low‐crossover centres relative to the high‐crossover peripheries of chromosomes (“Chromosome Centre‐Biased Differentiation”, CCBD). Using simulated and empirical data, we then show that strong CCBD between populations can provide evidence of polygenic adaptive divergence with a phase of gene flow. We further demonstrate that chromosome‐scale heterogeneity in crossover rate impacts analyses beyond that of population differentiation, including the inference of phylogenies and parallel adaptive evolution among populations, the detection of genetic loci under selection, and the interpretation of the strength of selection on genomic regions. Overall, our results call for a greater appreciation of chromosome‐scale heterogeneity in crossover rate in evolutionary genomics. 相似文献
156.
Wittgens Andreas Kovacic Filip Müller Markus Michael Gerlitzki Melanie Santiago-Schübel Beatrix Hofmann Diana Tiso Till Blank Lars Mathias Henkel Marius Hausmann Rudolf Syldatk Christoph Wilhelm Susanne Rosenau Frank 《Applied microbiology and biotechnology》2017,101(7):2865-2878
Applied Microbiology and Biotechnology - The human pathogenic bacterium Pseudomonas aeruginosa produces rhamnolipids, glycolipids with functions for bacterial motility, biofilm formation, and... 相似文献
157.
Florin G. Horhat Fuat Gundogdu Laurentiu V. David Eugen S. Boia Laurentiu Pirtea Razvan Horhat Alexandru Cucui-Cozma Ioana Ciuca Mircea Diaconu Razvan Nitu Monica Licker Delia I. Horhat Alexandru F. Rogobete Marius L. Moise Calin Tataru 《Biochemical genetics》2017,55(3):204-211
A high percentage of critical patients are found to develop acute respiratory distress syndrome (ARDS). Several studies have reported high mortality rates in these cases which are most frequently associated with multiple organ dysfunctions syndrome. Lately, many efforts have been made to evaluate and monitor ARDS in critical patients. In this regard, the assessment of genetic polymorphisms responsible for developing ARDS present as a challenge and are considered future biomarkers. Early detection of the specific polymorphic gene responsible for ARDS in critically ill patients can prove to be a useful tool in the future, able to help decrease the mortality rates in these cases. Moreover, identifying the genetic polymorphism in these patients can help in the implementation of a personalized intensive therapy scheme for every type of patient, based on its genotype. 相似文献
158.
Fabio?NikolayEmail authorView authors OrcID profile Marius?Pesavento George?Kritikos Nassos?Typas 《EURASIP Journal on Bioinformatics and Systems Biology》2017,2017(1):10
In this paper, we consider the problem of learning the genetic interaction map, i.e., the topology of a directed acyclic graph (DAG) of genetic interactions from noisy double-knockout (DK) data. Based on a set of well-established biological interaction models, we detect and classify the interactions between genes. We propose a novel linear integer optimization program called the Genetic-Interactions-Detector (GENIE) to identify the complex biological dependencies among genes and to compute the DAG topology that matches the DK measurements best. Furthermore, we extend the GENIE program by incorporating genetic interaction profile (GI-profile) data to further enhance the detection performance. In addition, we propose a sequential scalability technique for large sets of genes under study, in order to provide statistically significant results for real measurement data. Finally, we show via numeric simulations that the GENIE program and the GI-profile data extended GENIE (GI-GENIE) program clearly outperform the conventional techniques and present real data results for our proposed sequential scalability technique. 相似文献
159.
Piptadenin,a Novel 3,4‐Secooleanane Triterpene and Piptadenamide,a New Ceramide from the Stem Bark of Piptadeniastrum africanum (Hook.f.) Brenan
下载免费PDF全文
![点击此处可从《化学与生物多样性》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Amadou Dawé Marius Mbiantcha Yannick Fongang William Yosseu Nana Fawai Yakai Gilbert Ateufack Muhammad Ali Shaiq Iqbal Lubna Mehreen Lateef Bonaventure Tchaleu Ngadjui 《化学与生物多样性》2017,14(2)
Piptadenin ( 1 ), a new triterpene along with piptadenamide ( 10 ), a new ceramide, have been isolated from the AcOEt‐soluble fraction of the MeOH extract of the stem bark of Piptadeniastrum africanum along with nine known compounds, 1‐O‐[(3β,22β)‐3,22‐dihydroxy‐28‐oxoolean‐12‐en‐28‐yl]‐β‐d ‐glucopyranose ( 2 ), 22β‐hydroxyoleanic acid ( 3 ), oleanic acid ( 4 ), lupeol ( 5 ), betulinic acid ( 6 ), 5α‐stigmasta‐7,22‐dien‐3β‐ol ( 7 ), 5α‐stigmasta‐7,22‐dien‐3‐one ( 8 ), (3β)‐stigmast‐5‐en‐3‐yl β‐d ‐glucopyranoside ( 9 ) and 2,3‐dihydroxypropyl hexacosanoate ( 11 ). Except for compound 11 , all the isolated compounds are reported for the first time from this plant. The structures of the isolated compounds were elucidated by spectroscopic data including 1D and 2D NMR. The pure compounds 1 – 11 were subjected to the pharmacological screening and compounds 2 , 5 – 7 and 9 exhibited potent urease inhibitory activity with IC50 value of 25.8, 28.9, 30.1, 31.8 and 32.7 μm , respectively, whereas compound 1 showed moderate activity (IC50 = 98.7 μm ). The potent urease inhibitory activity supplemented the previous literature reports and medicinal uses of this plant. 相似文献
160.
A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types 总被引:1,自引:0,他引:1
Wernig M Lengner CJ Hanna J Lodato MA Steine E Foreman R Staerk J Markoulaki S Jaenisch R 《Nature biotechnology》2008,26(8):916-924
The study of induced pluripotency is complicated by the need for infection with high-titer retroviral vectors, which results in genetically heterogeneous cell populations. We generated genetically homogeneous 'secondary' somatic cells that carry the reprogramming factors as defined doxycycline (dox)-inducible transgenes. These cells were produced by infecting fibroblasts with dox-inducible lentiviruses, reprogramming by dox addition, selecting induced pluripotent stem cells and producing chimeric mice. Cells derived from these chimeras reprogram upon dox exposure without the need for viral infection with efficiencies 25- to 50-fold greater than those observed using direct infection and drug selection for pluripotency marker reactivation. We demonstrate that (i) various induction levels of the reprogramming factors can induce pluripotency, (ii) the duration of transgene activity directly correlates with reprogramming efficiency, (iii) cells from many somatic tissues can be reprogrammed and (iv) different cell types require different induction levels. This system facilitates the characterization of reprogramming and provides a tool for genetic or chemical screens to enhance reprogramming. 相似文献