全文获取类型
收费全文 | 569篇 |
免费 | 107篇 |
专业分类
676篇 |
出版年
2017年 | 9篇 |
2015年 | 12篇 |
2014年 | 17篇 |
2013年 | 18篇 |
2012年 | 18篇 |
2011年 | 17篇 |
2010年 | 21篇 |
2009年 | 18篇 |
2008年 | 22篇 |
2007年 | 13篇 |
2006年 | 19篇 |
2005年 | 26篇 |
2004年 | 26篇 |
2003年 | 9篇 |
2002年 | 25篇 |
2001年 | 17篇 |
2000年 | 16篇 |
1999年 | 10篇 |
1998年 | 15篇 |
1997年 | 11篇 |
1996年 | 12篇 |
1995年 | 9篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 14篇 |
1991年 | 18篇 |
1990年 | 18篇 |
1989年 | 11篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 14篇 |
1985年 | 6篇 |
1984年 | 9篇 |
1983年 | 11篇 |
1982年 | 18篇 |
1981年 | 9篇 |
1980年 | 8篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 8篇 |
1976年 | 6篇 |
1975年 | 14篇 |
1974年 | 10篇 |
1973年 | 8篇 |
1972年 | 7篇 |
1970年 | 5篇 |
1969年 | 5篇 |
1968年 | 10篇 |
1967年 | 7篇 |
1966年 | 9篇 |
排序方式: 共有676条查询结果,搜索用时 15 毫秒
91.
The computer-aided detection of artefacts became an essential task with increasing automation of quantitative electroencephalogram (EEG) analysis during anaesthesiological applications. The different algorithms published so far required individual manual adjustment or have been based on limited decision criteria. In this study, we developed an artificial neural networks-(ANN-)aided method for automated detection of artefacts and EEG suppression periods. 72 hr EEG recorded before, during and after anaesthesia with propofol have been evaluated. Selected parameterized patterns of 0.25 s length were used to train the ANN (22 input, 8 hidden and 4 output neurons) with error back propagation. The detection performance of the ANN-aided method was tested with processing epochs between 1 to10 s. Related to examiner EEG evaluation, the average detection performance of the method was 72% sensitivity and 80% specificity for artefacts and 90% sensitivity and 92% specificity for EEG suppression. The improvement in signal-to-noise ratio with automated artefact processing was 1.39 times for the spectral edge frequency 95 (SEF95) and 1.89 times for the approximate entropy (ApEn). We conclude that ANN-aided preprocessing provide an useful tool for automated EEG evaluation in anaesthesiological applications. 相似文献
92.
93.
94.
Sebastian Ullrich Phillip Bremer Christine Neumann-Grutzeck Helge Otto Christoph Rüther Cay Uwe von Seydewitz Gerd Peter Meyer Keihan Ahmadi-Simab Joachim R?ther Barbara Hogan Wolfgang Schwenk Roman Fischbach J?rg Caselitz Jochen Puttfarcken Susanne Huggett Petra Tiedeken Jordan Pober Nancy C. Kirkiles-Smith Friedrich Hagenmüller 《PloS one》2013,8(2)
Objectives
Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli (STEC/EHEC) is one of the most common causes of Haemolytic Uraemic Syndrome (HUS) related to infectious haemorrhagic colitis. Nearly all recommendations on clinical management of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first to be caused by the serotype O104:H4. This EHEC strain was found to carry genetic features of Entero Aggregative E. coli (EAEC) and extended spectrum β lactamase (ESBL). We report symptoms and complications in patients at one of the most affected centres of the 2011 EHEC O104 outbreak in Northern Germany.Methods
The courses of patients admitted to our hospital due to bloody diarrhoea with suspected EHEC O104 infection were recorded prospectively. These data include the patients’ histories, clinical findings, and complications.Results
EHEC O104 infection was confirmed in 61 patients (female = 37; mean age: 44±2 years). The frequency of HUS was 59% (36/61) in our cohort. An enteric colonisation with co-pathogens was found in 57%. Thirty-one (51%) patients were treated with plasma-separation/plasmapheresis, 16 (26%) with haemodialysis, and 7 (11%) with Eculizumab. Patients receiving antibiotic treatment (n = 37; 61%) experienced no apparent change in their clinical course. Twenty-six (43%) patients suffered from neurological symptoms. One 83-year-old patient died due to comorbidities after HUS was successfully treated.Conclusions
EHEC O104:H4 infections differ markedly from earlier reports on O157:H7 induced enterocolitis in regard to epidemiology, symptomatology, and frequency of complications. We recommend a standard of practice for clinical monitoring and support the renaming of EHEC O104:H4 syndrome as “EAHEC disease”. 相似文献95.
Gangliosides Inhibit Platelet-Derived Growth Factor-Stimulated Receptor Dimerization in Human Glioma U-1242MG and Swiss 3T3 Cells 总被引:2,自引:1,他引:2
Abstract: We previously showed that gangliosides inhibit DNA synthesis in Swiss 3T3 cells stimulated with platelet-derived growth factor (PDGF) in a dose-responsive manner. This correlated with the inhibitory effects of several gangliosides (except GM3) on tyrosine phosphorylation of the PDGF receptor (PDGFR). [35 S]Methionine-labeled Swiss 3T3 cells were incubated either with or without gangliosides and stimulated with PDGF, and proteins were cross-linked with bis(sulfosuccinimidyl) suberate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that two protein bands (170 and 350 kDa) were specifically immunoprecipitated with an anti-PDGFR antibody. Using both Swiss 3T3 and human glioma U-1242MG cells, western blots with anti-PDGFR and anti-phosphotyrosine antibodies confirmed that these bands were the PDGFR monomer and dimer, respectively, and that phosphotyrosine was present in these bands only after cells were stimulated with PDGF. Of the gangliosides tested, GM1, GM2, GD1a, GD1b, GD3, and GT1b, but not GM3, inhibited the formation of the 350-kDa band. These results demonstrate that all gangliosides tested, except GM3, probably inhibit PDGF-mediated growth by preventing dimerization of PDGFR monomers. Loss of more complex gangliosides in human gliomas would permit unregulated activation of the PDGFR, contributing to uncontrolled growth stimulation. We propose that ganglioside inhibition of receptor dimerization is a novel mechanism for regulating and coordinating several trophic factor-mediated cell functions. 相似文献
96.
Modulation of antibody galactosylation through feeding of uridine, manganese chloride, and galactose
Gramer MJ Eckblad JJ Donahue R Brown J Shultz C Vickerman K Priem P van den Bremer ET Gerritsen J van Berkel PH 《Biotechnology and bioengineering》2011,108(7):1591-1602
Through process transfer and optimization for increased antibody production to 3 g/L for a GS-CHO cell line, an undesirable drop in antibody Fc galactosylation was observed. Uridine (U), manganese chloride (M), and galactose (G), constituents involved in the intracellular galactosylation process, were evaluated in 2-L bioreactors for their potential to specifically increase antibody galactosylation. These components were placed in the feed medium at proportionally increasing concentrations from 0 to 20 × UMG, where a 1× concentration of U was 1 mM, a 1× concentration of M was 0.002 mM, and a 1× concentration of G was 5 mM. Antibody galactosylation increased rapidly from 3% at 0× UMG up to 21% at 8× UMG and then more slowly to 23% at 20× UMG. The increase was primarily due to a shift from G0F to G1F, with minimal impact on other glycoforms or product quality attributes. Cell culture performance was largely not impacted by addition of up to 20× UMG except for suppression of glucose consumption and lactate production at 16 and 20× UMG and a slight drop in antibody concentration at 20× UMG. Higher accumulation of free galactose in the medium was observed at 8× UMG and above, coincident with achieving the plateau of maximal galactosylation. A concentration of 4× UMG resulted in achieving the target of 18% galactosylation at 2-L scale, a result that was reproduced in a 1,000-L run. Follow-up studies to evaluate the addition of each component individually up to 12× concentration revealed that the effect was synergistic; the combination of all three components gave a higher level of galactosylation than addition of the each effect independently. The approach was found generally useful since a second cell line responded similarly, with an increase in galactosylation from 5% to 29% from 0 to 8× UMG and no further increase or impact on culture performance up to 12× UMG. These results demonstrate a useful approach to provide exact and specific control of antibody galactosylation through manipulation of the concentrations of uridine, manganese chloride, and galactose in the cell culture medium. 相似文献
97.
98.
Mari Källersjö James S. Farris Mark W. Chase Birgitta Bremer Michael F. Fay Christopher J. Humphries Gitte Petersen Ole Seberg Kåre Bremer 《Plant Systematics and Evolution》1998,213(3-4):259-287
The ever-larger data matrices resulting from continuing improvements in DNA sequencing techniques require faster and more efficient methods of phylogenetic analysis. Here we explore a promising new method, parsimony jackknifing, by analyzing a matrix comprising 2538 sequences of the chloroplast generbcL. The sequences included cover a broad taxonomic range, from cyanobacteria to flowering plants. Several parsimony jackknife analyses were performed, both with and without branch-swapping and multiple random addition sequences: 1) including all positions; 2) including only first and second codon positions; 3) including only third positions; and 4) using only transversions. The best resolution was obtained using all positions. Removal of third positions or transitions led to massive loss of resolution, although using only transversions somewhat improved basal resolution. While branch-swapping improved both resolution and the support found for several groups, most of the groups could be recovered by faster simple analyses. Designed to eliminate groups poorly supported by the data, parsimony jackknifing recognizes 1400 groups on the basis of allrbcL positions. These include major taxa such as green plants, land plants, flowering plants, monocots and eudicots. We include appendices of supported angiosperm families, as well as larger groups. 相似文献
99.
Magnetic resonance imaging (MRI) has evolved into a sophisticated, noninvasive imaging modality capable of high-resolution anatomical and functional characterization of transgenic animals. To expand the capabilities MRI, we have developed a novel MR signal amplification (MRamp) strategy based on enzyme-mediated polymerization of paramagnetic substrates into oligomers of higher magnetic relaxtivity. The substrates consist of chelated gadolinium covalently bound to phenols, which then serve as electron donors during enzymatic hydrogen peroxide reduction by peroxidase. The converted monomers undergo rapid condensation into paramagnetic oligomers leading to a threefold increase in atomic relaxtivity (R1/Gd). The observed relaxtivity changes are largely due to an increase in the rotational correlation time tau r of the lanthanide. Three applications of the developed system are demonstrated: (1) imaging of nanomolar amounts of an oxidoreductase (peroxidase); (2) detection of a model ligand using an enzyme-linked immunoadsorbent assay format; and (3) imaging of E-selectin on the surface of endothelial cells probed for with an anti-E-selectin-peroxidase conjugate. The development of "enzyme sensing" probes is expected to have utility for a number of applications including in vivo detection of specific molecular targets. One particular advantage of the MRamp technique is that the same paramagnetic substrate can be potentially used to identify different molecular targets by attaching enzymes to various antibodies or other target-seeking molecules. 相似文献
100.
Patricia R Facciotti Rose EG Rici Durvanei A Maria Marcelo Bertolini Carlos E Ambrósio Maria A Miglino 《Reproductive biology and endocrinology : RB&E》2009,7(1):25-7