全文获取类型
收费全文 | 1080篇 |
免费 | 79篇 |
专业分类
1159篇 |
出版年
2023年 | 4篇 |
2022年 | 17篇 |
2021年 | 32篇 |
2020年 | 16篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 20篇 |
2016年 | 28篇 |
2015年 | 54篇 |
2014年 | 56篇 |
2013年 | 69篇 |
2012年 | 74篇 |
2011年 | 90篇 |
2010年 | 42篇 |
2009年 | 44篇 |
2008年 | 62篇 |
2007年 | 75篇 |
2006年 | 48篇 |
2005年 | 46篇 |
2004年 | 46篇 |
2003年 | 32篇 |
2002年 | 47篇 |
2001年 | 9篇 |
2000年 | 7篇 |
1999年 | 11篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 9篇 |
1992年 | 6篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1968年 | 3篇 |
1892年 | 3篇 |
排序方式: 共有1159条查询结果,搜索用时 15 毫秒
41.
de Jong RM Bazzacco P Poelarends GJ Johnson WH Kim YJ Burks EA Serrano H Thunnissen AM Whitman CP Dijkstra BW 《The Journal of biological chemistry》2007,282(4):2440-2449
The bacterial degradation pathways for the nematocide 1,3-dichloropropene rely on hydrolytic dehalogenation reactions catalyzed by cis- and trans-3-chloroacrylic acid dehalogenases (cis-CaaD and CaaD, respectively). X-ray crystal structures of native cis-CaaD and cis-CaaD inactivated by (R)-oxirane-2-carboxylate were elucidated. They locate four known catalytic residues (Pro-1, Arg-70, Arg-73, and Glu-114) and two previously unknown, potential catalytic residues (His-28 and Tyr-103'). The Y103F and H28A mutants of these latter two residues displayed reductions in cis-CaaD activity confirming their importance in catalysis. The structure of the inactivated enzyme shows covalent modification of the Pro-1 nitrogen atom by (R)-2-hydroxypropanoate at the C3 position. The interactions in the complex implicate Arg-70 or a water molecule bound to Arg-70 as the proton donor for the epoxide ring-opening reaction and Arg-73 and His-28 as primary binding contacts for the carboxylate group. This proposed binding mode places the (R)-enantiomer, but not the (S)-enantiomer, in position to covalently modify Pro-1. The absence of His-28 (or an equivalent) in CaaD could account for the fact that CaaD is not inactivated by either enantiomer. The cis-CaaD structures support a mechanism in which Glu-114 and Tyr-103' activate a water molecule for addition to C3 of the substrate and His-28, Arg-70, and Arg-73 interact with the C1 carboxylate group to assist in substrate binding and polarization. Pro-1 provides a proton at C2. The involvement of His-28 and Tyr-103' distinguishes the cis-CaaD mechanism from the otherwise parallel CaaD mechanism. The two mechanisms probably evolved independently as the result of an early gene duplication of a common ancestor. 相似文献
42.
Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts 总被引:2,自引:0,他引:2
Beckonert O Keun HC Ebbels TM Bundy J Holmes E Lindon JC Nicholson JK 《Nature protocols》2007,2(11):2692-2703
Metabolic profiling, metabolomic and metabonomic studies mainly involve the multicomponent analysis of biological fluids, tissue and cell extracts using NMR spectroscopy and/or mass spectrometry (MS). We summarize the main NMR spectroscopic applications in modern metabolic research, and provide detailed protocols for biofluid (urine, serum/plasma) and tissue sample collection and preparation, including the extraction of polar and lipophilic metabolites from tissues. 1H NMR spectroscopic techniques such as standard 1D spectroscopy, relaxation-edited, diffusion-edited and 2D J-resolved pulse sequences are widely used at the analysis stage to monitor different groups of metabolites and are described here. They are often followed by more detailed statistical analysis or additional 2D NMR analysis for biomarker discovery. The standard acquisition time per sample is 4-5 min for a simple 1D spectrum, and both preparation and analysis can be automated to allow application to high-throughput screening for clinical diagnostic and toxicological studies, as well as molecular phenotyping and functional genomics. 相似文献
43.
Due to its inherent asymmetry, competition for light is thought to cause loss of diversity from eutrophied systems. However, most of the work on this topic in grasslands has been phenomenological and has not measured light directly. We present the results of one of the few mechanistic experiments investigating the outcome of short-term competition using measurements of light interception from monocultures of five perennial grass species grown under fertilized and irrigated conditions. We found that the level of incident light intercepted by each species in monoculture, a direct measure of resource-reduction ability, was an excellent predictor of the relative competitive effect in pairwise mixtures. Competition for light was asymmetric in relation to differences in light intercepting ability. Our results are consistent with the idea that when light is a limiting resource, competition between species for this resource can be asymmetric, contributing to high dominance and low diversity. 相似文献
44.
45.
46.
Leng Yu Wang Hao de Lucio Mario Gomez Hector 《Biomechanics and modeling in mechanobiology》2022,21(6):1825-1840
Biomechanics and Modeling in Mechanobiology - Subcutaneous injection of therapeutic monoclonal antibodies (mAbs) has gained increasing interest in the pharmaceutical industry. The transport,... 相似文献
47.
Marco Savioli Lorenzo Antonelli Gianfranco Bocchinfuso Francesca Cavalieri Rita Cimino Emanuela Gatto Ernesto Placidi Julio Raul Fernandez Masso Hilda Garay Perez Hector Santana Maribel Guerra-Vallespi Mariano Venanzi 《Journal of peptide science》2022,28(1):e3356
Synthetic therapeutic peptides (STP) are intensively studied as new-generation drugs, characterized by high purity, biocompatibility, selectivity and stereochemical control. However, most of the studies are focussed on the bioactivity of STP without considering how the formulation actually used for therapy administration could alter the physico-chemical properties of the active principle. The aggregation properties of a 20-mer STP (Ac-His-Ala-Arg-Ile-Lys-D-Pro-Thr-Phe-Arg-Arg-D-Leu-Lys-Trp-Lys-Tyr-Lys-Gly-Lys-Phe-Trp-NH2), showing antitumor activity, were investigated by optical spectroscopy and atomic force microscopy imaging, as itself (CIGB552) and in its therapeutic formulation (CIGB552TF). It has found that the therapeutic formulation deeply affects the aggregation properties of the investigated peptide and the morphology of the aggregates formed on mica by deposition of CIGB552 and CIGB552TF millimolar solutions. Molecular dynamics simulations studied the first steps of CIGB552 aggregation under physiological ionic strength conditions (NaCl 150 mM), showing that peptide oligomers, from dimers to tetramers, are preferentially formed in this environment. Interestingly, cell viability assays performed on H-460 cell lines indicate a major antiproliferative activity of the peptide in its therapeutic formulation with respect to the peptide aqueous solution. 相似文献
48.
Tobias E. Hector Isobel Booksmythe 《Evolution; international journal of organic evolution》2019,73(4):858-859
Research predicting the impact and spread of infectious disease has been heavily influenced by the idea of an evolutionary trade‐off between a pathogen's virulence and its transmission rate. In a meta‐analysis of the key underlying relationships, Acevedo et al. (2019) highlight the surprising lack of empirical evidence for this influential hypothesis. 相似文献
49.
50.
DeLuca HF 《The Journal of steroid biochemistry and molecular biology》2004,(1-5):67-73
Five analogs of 19-nor-1alpha,25-dihydroxyvitamin D(3) are described that show highly selective and potent activities. The 2-methylene-19-nor-(20S)-1alpha25-dihydroxyvitamin D(3) (2MD) and its 2alpha-methyl sister are selectively active on the osteoblast. 2MD is bone anabolic and causes bone formation in vivo and in vitro and is being developed as a therapy for bone loss diseases such as osteoporosis. 2-Methylene-19-nor (20S)-bishomo-1alpha-hydroxypregnacalciferol (2BMP) has no activity on calcium in vivo while totally suppressing circulating parathyroid hormone. Its homologs, i.e. 2-methylene-19-nor-1alpha-hydroxy-homopregnacalciferol (2MP) and 2-methylene-19-nor-1alpha-hydroxypregnacalciferol (2MPC) act similarly but are either less selective (2MP) or not as potent (2MPC). These abbreviated side chain analogs will be developed for diseases where a rise in serum calcium is not desired, as for example, cancer, renal osteodystrophy, psoriasis and autoimmune diseases. 相似文献