全文获取类型
收费全文 | 774篇 |
免费 | 104篇 |
专业分类
878篇 |
出版年
2022年 | 9篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 16篇 |
2017年 | 23篇 |
2016年 | 23篇 |
2015年 | 34篇 |
2014年 | 33篇 |
2013年 | 35篇 |
2012年 | 67篇 |
2011年 | 53篇 |
2010年 | 37篇 |
2009年 | 30篇 |
2008年 | 44篇 |
2007年 | 44篇 |
2006年 | 36篇 |
2005年 | 37篇 |
2004年 | 31篇 |
2003年 | 37篇 |
2002年 | 41篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1999年 | 17篇 |
1998年 | 18篇 |
1997年 | 10篇 |
1996年 | 18篇 |
1995年 | 12篇 |
1994年 | 16篇 |
1993年 | 3篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 4篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1981年 | 14篇 |
1980年 | 4篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1969年 | 4篇 |
1967年 | 3篇 |
1966年 | 4篇 |
排序方式: 共有878条查询结果,搜索用时 11 毫秒
71.
72.
Gao G Smiesko M Schwardt O Gäthje H Kelm S Vedani A Ernst B 《Bioorganic & medicinal chemistry》2007,15(23):7459-7469
The synthesis of phenoxyphenyl, phenoxybenzyl, biphenyl, and phenyltriazole substituted sialic acid derivatives as mimics of the tri- and tetrasaccharide epitopes of GQ1balpha is described. These synthetically easily available sialosides show comparable or even enhanced affinity to MAG compared with the natural tri- and tetrasaccharide epitopes and form a new class of potential MAG antagonists. 相似文献
73.
Molecular imaging with targeted contrast ultrasound 总被引:22,自引:0,他引:22
Molecular imaging with contrast ultrasound relies on the detection of targeted microbubbles or other acoustically active nanoparticles. These microbubbles are retained in diseased tissue where they produce an acoustic signal because of their resonant properties in the ultrasound field. Targeting is accomplished either through manipulating the chemical properties of the microbubble shell or through conjugation of disease-specific ligands for the targeted molecule to the microbubble surface. As microbubbles cannot leave the intravascular space, the disease process must be characterized by molecular changes in the vascular compartment to be imaged. Inflammation, angiogenesis and thrombus formation are central pathophysiologic processes in many disease states and produce phenotypic changes in the vascular compartment. Thus, targeted contrast ultrasound in the future could aid in the diagnosis of such diverse diseases as atherosclerosis, transplant rejection and tumor-related angiogenesis. 相似文献
74.
Lutz B 《Molecular neurobiology》2007,36(1):92-101
The endocannabinoid system has emerged as a versatile neuromodulatory system, implicated in a plethora of physiological and
pathophysiological processes. Cannabinoid receptor type 1 (CB1 receptor) and endocannabinoids are widely distributed in the
brain. Their roles in learning and memory have been well documented, using rodents in various memory tests. Depending on the
test, the endocannabinoid system is required in the acquisition and/or extinction of memory. In particular, the activation
of CB1 receptor-mediated signaling is centrally involved in the facilitation of behavioral adaptation after the acquisition
of aversive memories. As several human psychiatric disorders, such as phobia, generalized anxiety disorders, and posttraumatic
stress disorder (PTSD) appear to involve aberrant memory processing and impaired adaptation to changed environmental conditions,
the hope has been fuelled that the endocannabinoid system might be a valuable therapeutic target for the treatment of these
disorders. This review summarizes the current data on the role of the endocannabinoid system in the modulation of extinction
learning. 相似文献
75.
76.
77.
Celestine?N.?Chi Dean?Strotz Roland?RiekEmail author Beat?V?geliEmail author 《Journal of biomolecular NMR》2015,62(1):63-69
The representation of a protein’s spatial sampling at atomic resolution is fundamental for understanding its function. NMR has been established as the best-suited technique toward this goal for small proteins. However, the accessible information content rapidly deteriorates with increasing protein size. We have recently demonstrated that for small proteins distance restraints with an accuracy smaller than 0.1 Å can be obtained by replacing traditional semi-quantitative Nuclear Overhauser Effects (NOEs) with exact NOEs (eNOE). The high quality of the data allowed us to calculate structural ensembles of the small model protein GB3 consisting of multiple rather than a single state. The analysis has been limited to small proteins because NOEs of spins with unresolved diagonal peaks cannot be used. Here we propose a simple approach to translate such NOEs into correct upper distance restraints, which opens access to larger biomolecules. We demonstrate that for 16 kDa cyclophilin A the collection of such restraints extends the original 1254 eNOEs to 3471. 相似文献
78.
Beat Ruffner Maria Péchy-Tarr Monica H?fte Guido Bloemberg Jürg Grunder Christoph Keel Monika Maurhofer 《BMC genomics》2015,16(1)
Background
Root-colonizing fluorescent pseudomonads are known for their excellent abilities to protect plants against soil-borne fungal pathogens. Some of these bacteria produce an insecticidal toxin (Fit) suggesting that they may exploit insect hosts as a secondary niche. However, the ecological relevance of insect toxicity and the mechanisms driving the evolution of toxin production remain puzzling.Results
Screening a large collection of plant-associated pseudomonads for insecticidal activity and presence of the Fit toxin revealed that Fit is highly indicative of insecticidal activity and predicts that Pseudomonas protegens and P. chlororaphis are exclusive Fit producers. A comparative evolutionary analysis of Fit toxin-producing Pseudomonas including the insect-pathogenic bacteria Photorhabdus and Xenorhadus, which produce the Fit related Mcf toxin, showed that fit genes are part of a dynamic genomic region with substantial presence/absence polymorphism and local variation in GC base composition. The patchy distribution and phylogenetic incongruence of fit genes indicate that the Fit cluster evolved via horizontal transfer, followed by functional integration of vertically transmitted genes, generating a unique Pseudomonas-specific insect toxin cluster.Conclusions
Our findings suggest that multiple independent evolutionary events led to formation of at least three versions of the Mcf/Fit toxin highlighting the dynamic nature of insect toxin evolution.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1763-2) contains supplementary material, which is available to authorized users. 相似文献79.
von der Lieth CW Freire AA Blank D Campbell MP Ceroni A Damerell DR Dell A Dwek RA Ernst B Fogh R Frank M Geyer H Geyer R Harrison MJ Henrick K Herget S Hull WE Ionides J Joshi HJ Kamerling JP Leeflang BR Lütteke T Lundborg M Maass K Merry A Ranzinger R Rosen J Royle L Rudd PM Schloissnig S Stenutz R Vranken WF Widmalm G Haslam SM 《Glycobiology》2011,21(4):493-502
The EUROCarbDB project is a design study for a technical framework, which provides sophisticated, freely accessible, open-source informatics tools and databases to support glycobiology and glycomic research. EUROCarbDB is a relational database containing glycan structures, their biological context and, when available, primary and interpreted analytical data from high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance experiments. Database content can be accessed via a web-based user interface. The database is complemented by a suite of glycoinformatics tools, specifically designed to assist the elucidation and submission of glycan structure and experimental data when used in conjunction with contemporary carbohydrate research workflows. All software tools and source code are licensed under the terms of the Lesser General Public License, and publicly contributed structures and data are freely accessible. The public test version of the web interface to the EUROCarbDB can be found at http://www.ebi.ac.uk/eurocarb. 相似文献
80.
Habenstein B Wasmer C Bousset L Sourigues Y Schütz A Loquet A Meier BH Melki R Böckmann A 《Journal of biomolecular NMR》2011,51(3):235-243
We present the de novo resonance assignments for the crystalline 33 kDa C-terminal domain of the Ure2 prion using an optimized
set of five 3D solid-state NMR spectra. We obtained, using a single uniformly 13C, 15N labeled protein sample, sequential chemical-shift information for 74% of the N, Cα, Cβ triples, and for 80% of further side-chain
resonances for these spin systems. We describe the procedures and protocols devised, and discuss possibilities and limitations
of the assignment of this largest protein assigned today by solid-state NMR, and for which no solution-state NMR shifts were
available. A comparison of the NMR chemical shifts with crystallographic data reveals that regions with high crystallographic
B-factors are particularly difficult to assign. While the secondary structure elements derived from the chemical shift data
correspond mainly to those present in the X-ray crystal structure, we detect an additional helical element and structural
variability in the protein crystal, most probably originating from the different molecules in the asymmetric unit, with the
observation of doubled resonances in several parts, including entire stretches, of the protein. Our results provide the point
of departure towards an atomic-resolution structural analysis of the C-terminal Ure2p domain in the context of the full-length
prion fibrils. 相似文献