全文获取类型
收费全文 | 898篇 |
免费 | 66篇 |
国内免费 | 1篇 |
出版年
2022年 | 5篇 |
2021年 | 8篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 9篇 |
2016年 | 18篇 |
2015年 | 22篇 |
2014年 | 39篇 |
2013年 | 58篇 |
2012年 | 76篇 |
2011年 | 59篇 |
2010年 | 49篇 |
2009年 | 28篇 |
2008年 | 48篇 |
2007年 | 48篇 |
2006年 | 45篇 |
2005年 | 50篇 |
2004年 | 54篇 |
2003年 | 36篇 |
2002年 | 53篇 |
2001年 | 12篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1998年 | 17篇 |
1997年 | 8篇 |
1996年 | 13篇 |
1995年 | 13篇 |
1994年 | 11篇 |
1993年 | 12篇 |
1992年 | 13篇 |
1991年 | 8篇 |
1990年 | 9篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 6篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1977年 | 4篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1969年 | 3篇 |
1952年 | 2篇 |
1855年 | 2篇 |
排序方式: 共有965条查询结果,搜索用时 15 毫秒
31.
Streptomyces michiganensis strain Tü 1074, was isolated from a Tunesian soil sample and produces in liquid medium an antibiotic active pigment complex. Besides mitomycin A the separation of this complex yielded a nonactive phenoxazone, which hitherto has not been described in the literature. In contrary to all known phenoxazones from microorganisms the new compound lacks a 2-amino-function. The production of this phenoxazone could be enhanced by optimizing the conditions of fermentation. 相似文献
32.
Citrate lyase (EC 4.1.3.6) was purified 38-fold from cell-free extracts of Streptococcus diacetilactis. The enzyme was homogeneous in analytical ultracentrifugation and polyacrylamide gel electrophoresis The final enzyme preparation contained acetate: HS-citrate lyase ligase—an acetylating enzyme which converts inactive HS-citrate lyase into enzymatically active acetyl-S-citrate lyase. This enzyme activity was purified 25-fold over the crude extract and seemed to be associated with citrate lyase. Partially purified citrate lyase from Leuconostoc citrovorum contained also its acetylating enzyme. Purified citrate lyases from Klebsiella aerogenes and Rhodopseudomonas gelatinosa were devoid of acetylating enzyme activity. The HS-form of citrate lyase from S. diacetilactis was completely acetylated and hence activated by incubation with ATP and acetate for 25 min at 25° C. The enzyme did not acetylate the HS-lyases from R. gelatinosa and K. aerogenes. In contrast to the citrate lyases from R. gelatinosa and K. aerogenes the enzymes from S. diacetilactis and L. citrovorum showed onlya very weak reaction inactivation. It is assumed that this is due to the association of the acetylating enzymes with these lyases. 相似文献
33.
Henrik Gislason Jeremy Collie Brian R. MacKenzie Anders Nielsen Maria de Fatima Borges Teresa Bottari Corina Chaves Andrey V. Dolgov Jakov Dul
i Daniel Duplisea Heino O. Fock Didier Gascuel Luís Gil de Sola Jan Geert Hiddink Remment ter Hofstede Igor Isajlovi Jnas Pll Jonasson Ole Jrgensen Kristjn Kristinsson Gudrun Marteinsdottir Hicham Masski Sanja Mati‐Skoko Mark R. Payne Melita Peharda Jakup Reinert Jn Slmundsson Cristina Silva Lilja Stefansdottir Francisco Velasco Nedo Vrgo
《Global Ecology and Biogeography》2020,29(5):842-856
34.
Jrg Bckelmann Karin Tremetsberger Kateina umberov Gudrun Kohl Heinrich Grausgruber Karl‐Georg Bernhardt 《Ecology and evolution》2020,10(8):3620-3635
Many ephemeral mudflat species, which rely on a soil seed bank to build up the next generation, are endangered in their natural habitat due to the widespread regulation of rivers. The aim of the present study was to elucidate the role of the soil seed bank and dispersal for the maintenance of genetic diversity in populations of near‐natural river habitats and anthropogenic habitats created by traditional fish farming practices using Cyperus fuscus as a model. Using microsatellite markers, we found no difference in genetic diversity levels between soil seed bank and above‐ground population and only moderate differentiation between the two fractions. One possible interpretation is the difference in short‐term selection during germination under specific conditions (glasshouse versus field) resulting in an ecological filtering of genotypes out of the reservoir in the soil. River populations harbored significantly more genetic diversity than populations from the anthropogenic pond types. We suggest that altered levels and patterns of dispersal together with stronger selection pressures and historical bottlenecks in anthropogenic habitats are responsible for the observed reduction in genetic diversity. Dispersal is also supposed to largely prohibit genetic structure across Europe, although there is a gradient in private allelic richness from southern Europe (high values) to northern, especially north‐western, Europe (low values), which probably relates to postglacial expansion out of southern and/or eastern refugia. 相似文献
35.
36.
Wietske Lambert Gudrun Rutsdottir Rasha Hussein Katja Bernfur Sven Kjellstr?m Cecilia Emanuelsson 《Cell stress & chaperones》2013,18(1):75-85
Small heat-shock protein chaperones are important players in the protein quality control system of the cell, because they can immediately respond to partially unfolded proteins, thereby protecting the cell from harmful aggregates. The small heat-shock proteins can form large polydisperse oligomers that are exceptionally dynamic, which is implicated in their function of protecting substrate proteins from aggregation. Yet the mechanism of substrate recognition remains poorly understood, and little is known about what parts of the small heat-shock proteins interact with substrates and what parts of a partially unfolded substrate protein interact with the small heat-shock proteins. The transient nature of the interactions that prevent substrate aggregation rationalize probing this interaction by crosslinking mass spectrometry. Here, we used a workflow with lysine-specific crosslinking and offline nano-liquid chromatography matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry to explore the interaction between the plant small heat-shock protein Hsp21 and a thermosensitive model substrate protein, malate dehydrogenase. The identified crosslinks point at an interaction between the disordered N-terminal region of Hsp21 and the C-terminal presumably unfolding part of the substrate protein. 相似文献
37.
Joanna Szkandera Michael Stotz Florian Eisner Gudrun Absenger Tatjana Stojakovic Hellmut Samonigg Peter Kornprat Renate Schaberl-Moser Wael AlZoughbi Anna Lena Ress Friederike Sophia Seggewies Armin Gerger Gerald Hoefler Martin Pichler 《PloS one》2013,8(11)
Background
With growing evidence on the role of inflammation in cancer biology, the presence of a systemic inflammatory response has been postulated as having prognostic significance in a wide range of cancer types. The derived neutrophil to lymphocyte ratio (dNLR), which represents an easily determinable potential prognostic marker in daily practise and clinical trials, has never been externally validated in pancreatic cancer (PC) patients.Methods
Data from 474 consecutive PC patients, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied.Results
We calculated by ROC analysis a cut-off value of 2.3 for the dNLR to be ideal to discriminate between patients’ survival in the whole cohort. Kaplan-Meier curve reveals a dNLR≥2.3 as a factor for decreased CSS in PC patients (p<0.001, log-rank test). An independent significant association between high dNLR≥2.3 and poor clinical outcome in multivariate analysis (HR = 1.24, CI95% = 1.01–1.51, p = 0.041) was identified.Conclusion
In the present study we confirmed elevated pre-treatment dNLR as an independent prognostic factor for clinical outcome in PC patients. Our data encourage independent replication in other series and settings of this easily available parameter as well as stratified analysis according to tumor resectability. 相似文献38.
Birte Plitzko Gudrun Ott Debora Reichmann Colin J. Henderson C. Roland Wolf Ralf Mendel Florian Bittner Bernd Clement Antje Havemeyer 《The Journal of biological chemistry》2013,288(28):20228-20237
The mitochondrial amidoxime reducing component mARC is a recently discovered molybdenum enzyme in mammals. mARC is not active as a standalone protein, but together with the electron transport proteins NADH-cytochrome b5 reductase (CYB5R) and cytochrome b5 (CYB5), it catalyzes the reduction of N-hydroxylated compounds such as amidoximes. The mARC-containing enzyme system is therefore considered to be responsible for the activation of amidoxime prodrugs. All hitherto analyzed mammalian genomes code for two mARC genes (also referred to as MOSC1 and MOSC2), which share high sequence similarities. By RNAi experiments in two different human cell lines, we demonstrate for the first time that both mARC proteins are capable of reducing N-hydroxylated substrates in cell metabolism. The extent of involvement is highly dependent on the expression level of the particular mARC protein. Furthermore, the mitochondrial isoform of CYB5 (CYB5B) is clearly identified as an essential component of the mARC-containing N-reductase system in human cells. The participation of the microsomal isoform (CYB5A) in N-reduction could be excluded by siRNA-mediated down-regulation in HEK-293 cells and knock-out in mice. Using heme-free apo-CYB5, the contribution of mitochondrial CYB5 to N-reductive catalysis was proven to strictly depend on heme. Finally, we created recombinant CYB5B variants corresponding to four nonsynonymous single nucleotide polymorphisms (SNPs). Investigated mutations of the heme protein seemed to have no significant impact on N-reductive activity of the reconstituted enzyme system. 相似文献
39.
40.
Gudrun Lisa Bovenkamp Ulrike Zanzen Katla Sai Krishna Josef Hormes Alexander Prange 《Applied and environmental microbiology》2013,79(20):6385-6390
Silver ions are widely used as antibacterial agents, but the basic molecular mechanism of this effect is still poorly understood. X-ray absorption near-edge structure (XANES) spectroscopy at the Ag LIII, S K, and P K edges reveals the chemical forms of silver in Staphylococcus aureus and Escherichia coli (Ag+ treated). The Ag LIII-edge XANES spectra of the bacteria are all slightly different and very different from the spectra of silver ions (silver nitrate and silver acetate), which confirms that a reaction occurs. Death or inactivation of bacteria was observed by plate counting and light microscopy. Silver bonding to sulfhydryl groups (Ag-S) in cysteine and Ag-N or Ag-O bonding in histidine, alanine, and dl-aspartic acid was detected by using synthesized silver-amino acids. Significantly lower silver-cysteine content, coupled with higher silver-histidine content, in Gram-positive S. aureus and Listeria monocytogenes cells indicates that the peptidoglycan multilayer could be buffering the biocidal effect of silver on Gram-positive bacteria, at least in part. Bonding of silver to phosphate groups was not detected. Interaction with DNA or proteins can occur through Ag-N bonding. The formation of silver-cysteine can be confirmed for both bacterial cell types, which supports the hypothesis that enzyme-catalyzed reactions and the electron transport chain within the cell are disrupted. 相似文献