全文获取类型
收费全文 | 11008篇 |
免费 | 970篇 |
国内免费 | 5篇 |
出版年
2023年 | 45篇 |
2022年 | 85篇 |
2021年 | 180篇 |
2020年 | 115篇 |
2019年 | 148篇 |
2018年 | 193篇 |
2017年 | 171篇 |
2016年 | 321篇 |
2015年 | 477篇 |
2014年 | 567篇 |
2013年 | 668篇 |
2012年 | 877篇 |
2011年 | 866篇 |
2010年 | 536篇 |
2009年 | 501篇 |
2008年 | 686篇 |
2007年 | 692篇 |
2006年 | 637篇 |
2005年 | 652篇 |
2004年 | 645篇 |
2003年 | 587篇 |
2002年 | 565篇 |
2001年 | 104篇 |
2000年 | 69篇 |
1999年 | 115篇 |
1998年 | 179篇 |
1997年 | 111篇 |
1996年 | 96篇 |
1995年 | 97篇 |
1994年 | 100篇 |
1993年 | 90篇 |
1992年 | 68篇 |
1991年 | 59篇 |
1990年 | 43篇 |
1989年 | 46篇 |
1988年 | 43篇 |
1987年 | 44篇 |
1986年 | 36篇 |
1985年 | 49篇 |
1984年 | 36篇 |
1983年 | 50篇 |
1982年 | 63篇 |
1981年 | 41篇 |
1980年 | 25篇 |
1979年 | 33篇 |
1978年 | 35篇 |
1977年 | 19篇 |
1976年 | 20篇 |
1975年 | 16篇 |
1973年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
992.
The genome of Syntrophorhabdus aromaticivorans strain UI provides new insights for syntrophic aromatic compound metabolism and electron flow
下载免费PDF全文
![点击此处可从《Environmental microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Masaru K. Nobu Takashi Narihiro Tamaki Hideyuki Yan‐Ling Qiu Yuji Sekiguchi Tanja Woyke Lynne Goodwin Karen W. Davenport Yoichi Kamagata Wen‐Tso Liu 《Environmental microbiology》2015,17(12):4861-4872
How aromatic compounds are degraded in various anaerobic ecosystems (e.g. groundwater, sediments, soils and wastewater) is currently poorly understood. Under methanogenic conditions (i.e. groundwater and wastewater treatment), syntrophic metabolizers are known to play an important role. This study explored the draft genome of Syntrophorhabdus aromaticivorans strain UI and identified the first syntrophic phenol‐degrading phenylphosphate synthase (PpsAB) and phenylphosphate carboxylase (PpcABCD) and syntrophic terephthalate‐degrading decarboxylase complexes. The strain UI genome also encodes benzoate degradation through hydration of the dienoyl‐coenzyme A intermediate as observed in Geobacter metallireducens and Syntrophus aciditrophicus. Strain UI possesses electron transfer flavoproteins, hydrogenases and formate dehydrogenases essential for syntrophic metabolism. However, the biochemical mechanisms for electron transport between these H2/formate‐generating proteins and syntrophic substrate degradation remain unknown for many syntrophic metabolizers, including strain UI. Analysis of the strain UI genome revealed that heterodisulfide reductases (HdrABC), which are poorly understood electron transfer genes, may contribute to syntrophic H2 and formate generation. The genome analysis further identified a putative ion‐translocating ferredoxin : NADH oxidoreductase (IfoAB) that may interact with HdrABC and dissimilatory sulfite reductase gamma subunit (DsrC) to perform novel electron transfer mechanisms associated with syntrophic metabolism. 相似文献
993.
Proteomics of Colwellia psychrerythraea at subzero temperatures – a life with limited movement,flexible membranes and vital DNA repair
下载免费PDF全文
![点击此处可从《Environmental microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Karen A. Cameron Emma Timmins‐Schiffman Karen Junge 《Environmental microbiology》2015,17(7):2319-2335
The mechanisms that allow psychrophilic bacteria to remain metabolically active at subzero temperatures result from form and function of their proteins. We present first proteomic evidence of physiological changes of the marine psychrophile Colwellia psychrerythraea 34H (Cp34H) after exposure to subzero temperatures (?1, and ?10°C in ice) through 8 weeks. Protein abundance was compared between different treatments to understand the effects of temperature and time, independently and jointly, within cells transitioning to, and being maintained in ice. Parallel [3H]‐leucine and [3H]–thymidine incubations indicated active protein and DNA synthesis to ?10°C. Mass spectrometry‐based proteomics identified 1763 proteins across four experimental treatments. Proteins involved in osmolyte regulation and polymer secretion were found constitutively present across all treatments, suggesting that they are required for metabolic success below 0°C. Differentially abundant protein groups indicated a reallocation of resources from DNA binding to DNA repair and from motility to chemo‐taxis and sensing. Changes to iron and nitrogen metabolism, cellular membrane structures, and protein synthesis and folding were also revealed. By elucidating vital strategies during life in ice, this study provides novel insight into the extensive molecular adaptations that occur in cold‐adapted marine organisms to sustain cellular function in their habitat. 相似文献
994.
995.
The cavefish morph of the Mexican tetra (Astyanax mexicanus) is blind at adult stage, although an eye that includes a retina and a lens develops during embryogenesis. There are, however, two major defects in cavefish eye development. One is lens apoptosis, a phenomenon that is indirectly linked to the expansion of ventral midline sonic hedgehog (Shh) expression during gastrulation and that induces eye degeneration. The other is the lack of the ventral quadrant of the retina. Here, we show that such ventralisation is not extended to the entire forebrain because fibroblast growth factor 8 (Fgf8), which is expressed in the forebrain rostral signalling centre, is activated 2 hours earlier in cavefish embryos than in their surface fish counterparts, in response to stronger Shh signalling in cavefish. We also show that neural plate patterning and morphogenesis are modified in cavefish, as assessed by Lhx2 and Lhx9 expression. Inhibition of Fgf receptor signalling in cavefish with SU5402 during gastrulation/early neurulation mimics the typical surface fish phenotype for both Shh and Lhx2/9 gene expression. Fate-mapping experiments show that posterior medial cells of the anterior neural plate, which lack Lhx2 expression in cavefish, contribute to the ventral quadrant of the retina in surface fish, whereas they contribute to the hypothalamus in cavefish. Furthermore, when Lhx2 expression is rescued in cavefish after SU5402 treatment, the ventral quadrant of the retina is also rescued. We propose that increased Shh signalling in cavefish causes earlier Fgf8 expression, a crucial heterochrony that is responsible for Lhx2 expression and retina morphogenesis defect. 相似文献
996.
Netrins are secreted proteins that were first identified as guidance cues, directing cell and axon migration during neural development. Subsequent findings have demonstrated that netrins can influence the formation of multiple tissues, including the vasculature, lung, pancreas, muscle and mammary gland, by mediating cell migration, cell-cell interactions and cell-extracellular matrix adhesion. Recent evidence also implicates the ongoing expression of netrins and netrin receptors in the maintenance of cell-cell organisation in mature tissues. Here, we review the mechanisms involved in netrin signalling in vertebrate and invertebrate systems and discuss the functions of netrin signalling during the development of neural and non-neural tissues. 相似文献
997.
Alethia A. Hostetter Michelle L. Miranda Victoria J. DeRose Karen L. McFarlane Holman 《Journal of biological inorganic chemistry》2011,16(8):1177-1185
[ImH][trans-RuIIICl4(DMSO)(Im)] (where DMSO is dimethyl sulfoxide and Im is imidazole) (NAMI-A) is an antimetastatic prodrug currently in phase
II clinical trials. The mechanisms of action of this and related Ru-based anticancer agents are not well understood, but several
cellular targets have been suggested. Although Ru has been observed to bind to DNA following in vitro NAMI-A exposure, little
is known about Ru–DNA interactions in vivo and even less is known about how this or related metallodrugs might influence cellular
RNA. In this study, Ru accumulation in cellular RNA was measured following treatment of Saccharomyces cerevisiae with NAMI-A. Drug-dependent growth and cell viability indicate relatively high tolerance, with approximately 40% cell death
occurring at 6 h for 450 μM NAMI-A. Significant dose-dependent accumulation of Ru in cellular RNA was observed by inductively coupled plasma mass spectrometry
measurements on RNA extracted from yeast treated with NAMI-A. In vitro, binding of Ru species to drug-treated model DNA and
RNA oligonucleotides at pH 6.0 and 7.4 was characterized by matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry in the presence and absence of the reductant ascorbate. The extent of Ru–nucleotide interactions increases slightly
with lower pH and significantly in the presence of ascorbate, with differences in observed species distribution. Taken together,
these studies demonstrate the accumulation of aquated and reduced derivatives of NAMI-A on RNA in vitro and in cellulo, and
enhanced binding with nucleic acid targets in a tumorlike acidic, reducing environment. To our knowledge, this is also the
first study to characterize NAMI-A treatment of S. cerevisiae, a genetically tractable model organism. 相似文献
998.
999.
Medicago truncatula mtpt4 mutants reveal a role for nitrogen in the regulation of arbuscule degeneration in arbuscular mycorrhizal symbiosis 总被引:1,自引:0,他引:1
Javot H Penmetsa RV Breuillin F Bhattarai KK Noar RD Gomez SK Zhang Q Cook DR Harrison MJ 《The Plant journal : for cell and molecular biology》2011,68(6):954-965
Plants acquire essential mineral nutrients such as phosphorus (P) and nitrogen (N) directly from the soil, but the majority of the vascular plants also gain access to these mineral nutrients through endosymbiotic associations with arbuscular mycorrhizal (AM) fungi. In AM symbiosis, the fungi deliver P and N to the root through branched hyphae called arbuscules. Previously we identified MtPT4, a Medicago truncatula phosphate transporter located in the periarbuscular membrane that is essential for symbiotic phosphate transport and for maintenance of the symbiosis. In mtpt4 mutants arbuscule degeneration occurs prematurely and symbiosis fails. Here, we show that premature arbuscule degeneration occurs in mtpt4 mutants even when the fungus has access to carbon from a nurse plant. Thus, carbon limitation is unlikely to be the primary cause of fungal death. Surprisingly, premature arbuscule degeneration is suppressed if mtpt4 mutants are deprived of nitrogen. In mtpt4 mutants with a low N status, arbuscule lifespan does not differ from that of the wild type, colonization of the mtpt4 root system occurs as in the wild type and the fungus completes its life cycle. Sulphur is another essential macronutrient delivered to the plant by the AM fungus; however, suppression of premature arbuscule degeneration does not occur in sulphur-deprived mtpt4 plants. The mtpt4 arbuscule phenotype is strongly correlated with shoot N levels. Analyses of an mtpt4-2 sunn-1 double mutant indicates that SUNN, required for N-mediated autoregulation of nodulation, is not involved. Together, the data reveal an unexpected role for N in the regulation of arbuscule lifespan in AM symbiosis. 相似文献
1000.
Simplified method for the collection, storage, and comet assay analysis of DNA damage in whole blood
Al-Salmani K Abbas HH Schulpen S Karbaschi M Abdalla I Bowman KJ So KK Evans MD Jones GD Godschalk RW Cooke MS 《Free radical biology & medicine》2011,51(3):719-725
Single-cell gel electrophoresis (comet assay) is one of the most common methods used to measure oxidatively damaged DNA in peripheral blood mononuclear cells (PBMC), as a biomarker of oxidative stress in vivo. However, storage, extraction, and assay workup of blood samples are associated with a risk of artifactual formation of damage. Previous reports using this approach to study DNA damage in PBMC have, for the most part, required the isolation of PBMC before immediate analysis or freezing in cryopreservative. This is very time-consuming and a significant drain on human resources. Here, we report the successful storage of whole blood in ~ 250 μl volumes, at − 80 °C, without cryopreservative, for up to 1 month without artifactual formation of DNA damage. Furthermore, this blood is amenable for direct use in both the alkaline and the enzyme-modified comet assay, without the need for prior isolation of PBMC. In contrast, storage of larger volumes (e.g., 5 ml) of whole blood leads to an increase in damage with longer term storage even at − 80 °C, unless a cryopreservative is present. Our “small volume” approach may be suitable for archived blood samples, facilitating analysis of biobanks when prior isolation of PBMC has not been performed. 相似文献