全文获取类型
收费全文 | 1489篇 |
免费 | 77篇 |
国内免费 | 42篇 |
出版年
2023年 | 9篇 |
2022年 | 24篇 |
2021年 | 16篇 |
2020年 | 27篇 |
2019年 | 34篇 |
2018年 | 51篇 |
2017年 | 51篇 |
2016年 | 27篇 |
2015年 | 38篇 |
2014年 | 94篇 |
2013年 | 135篇 |
2012年 | 53篇 |
2011年 | 93篇 |
2010年 | 73篇 |
2009年 | 80篇 |
2008年 | 81篇 |
2007年 | 100篇 |
2006年 | 63篇 |
2005年 | 59篇 |
2004年 | 60篇 |
2003年 | 47篇 |
2002年 | 37篇 |
2001年 | 37篇 |
2000年 | 20篇 |
1999年 | 23篇 |
1998年 | 18篇 |
1997年 | 19篇 |
1996年 | 24篇 |
1995年 | 12篇 |
1994年 | 14篇 |
1993年 | 12篇 |
1992年 | 11篇 |
1991年 | 6篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1985年 | 18篇 |
1984年 | 15篇 |
1983年 | 22篇 |
1982年 | 21篇 |
1981年 | 9篇 |
1980年 | 10篇 |
1979年 | 14篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1973年 | 3篇 |
1972年 | 2篇 |
排序方式: 共有1608条查询结果,搜索用时 15 毫秒
61.
Abstract A series of molecular dynamics simulations of liquid methanol has been carried out on a supernode transputer array. Four system sizes from 125 to 512 molecules have been considered, in order to study the effect of system size on the calculated structural, orientational and dynamic properties. The dielectric constant and the dielectric relaxation time are compared with experimental data. 相似文献
62.
Asieh Moodi Meissam Noroozifar Sona Niroomand 《Journal of biomolecular structure & dynamics》2013,31(8):937-950
To evaluate the biological preference of [Yb(phen)2(OH2)Cl3](H2O)2 (phen is 1,10-phenanthroline) for DNA, interaction of Yb(III) complex with DNA in Tris–HCl buffer is studied by various biophysical and spectroscopic techniques which reveal that the complex binds to DNA. The results of fluorescence titration reveal that [Yb(phen)2(OH2)Cl3](H2O)2 has strongly quenched in the presence of DNA. The binding site number n, apparent binding constant K b, and the Stern–Volmer quenching constant K SV are determined. ΔH 0, ΔS 0, and ΔG 0 are obtained based on the quenching constants and thermodynamic theory (ΔH 0?>?0, ΔS 0?>?0, and ΔG 0?<?0). The experimental results show that the Yb(III) complex binds to DNA by non-intercalative mode. Groove binding is the preferred mode of interaction for [Yb(phen)2(OH2)Cl3](H2O)2 to DNA. The DNA cleavage results show that in the absence of any reducing agent, Yb(III) complex can cleave DNA. The antimicrobial screening tests are also recorded and give good results in the presence of Yb(III) complex. 相似文献
63.
Robert L. Jernigan Akinori Sarai Bruce Shapiro Ruth Nussinov 《Journal of biomolecular structure & dynamics》2013,31(4):561-567
Abstract We propose some specific DNA conformations that explain, in terms of molecular conformations, the anomalous gel electrophoretic behavior of the sequences (VA4T4X)1, and (V2A3X2)1 where V and X are either G or C. Previously (J. Biomole. Struct. Dyn. 4, 41, 1986) we considered hydrophobic interactions a mong aliphatic hydrocarbon groups in A/T sequences. In the sequences (T)n · (A)n, the T's are slightly bent to yield structures with tightly stacked methyl groups along one side of the major groove. By folding together the two pairs of stacked methyls on the opposite sides of the major groove, TTAA might yield a relatively sharp bend. On this basis, we show below that the sequences (VT4A4X)1 might form a very tightly coiled super-helix whereas the sequences (VA4T4X)1 form a broad super-helix of radius ~ 120 A for i = 25. The sequence (V2A3T3X2)1 forms a slightly smaller radius super-helix. The time of passage through the gel has been taken to be inversely proportional to the smallesuiimension of the molecule. Specifically we are taking the ratio of the apparent molecular weight to the actual molecular weight to be related to the moment of inertia I1 about the smallest principal axis of the molecular conformation. We find a good fit to the experimental gel mobility data of Hagerman (2) if we assume this ratio to be proportional to (I1)1/5. 相似文献
64.
D. Jeya Sundara Sharmila K. Veluraja 《Journal of biomolecular structure & dynamics》2013,31(6):641-656
Abstract Molecular mechanics and molecular dynamics studies are performed to investigate the conformational preference of cell surface higher gangliosides (GT1A and GT1B) and their interaction with Cholera Toxin. The water mediated hydrogen bonding network exists between sugar residues in gangliosides. An integrated molecular modeling, molecular mechanics, and molecular dynamics calculation of cholera toxin complexed with GT1A and GT1B reveal that, the active site of cholera toxin can accommodate these higher gangliosides. Direct and water mediated hydrogen bonding interactions stabilize these binding modes and play an essential role in defining the order of specificity for different higher ganglioside towards cholera toxin. This study identifies that the binding site of cholera toxin is shallow and can accommodate a maximum of two NeuNAc residues. The NeuNAc binding site of cholera toxin may be crucial for the design of inhibitors that can prevent the infection of cholera. 相似文献
65.
Thomas C. Bishop 《Journal of biomolecular structure & dynamics》2013,31(6):673-685
Abstract All atom molecular dynamics simulations (10ns) of a nucleosome and of its 146 basepairs of DNA free in solution have been conducted. DNA helical parameters (Roll, Tilt, Twist, Shift, Slide, Rise) were extracted from each trajectory to compare the conformation, effective force constants, persistence length measures, and fluctuations of nucleosomal DNA to free DNA. The conformation of DNA in the nucleosome, as determined by helical parameters, is found to be largely within the range of thermally accessible values obtained for free DNA. DNA is found to be less flexible on the nucleosome than when free in solution, however such measures are length scale dependent. A method for disassembling and reconstructing the conformation and dynamics of the nucleosome using Fourier analysis is presented. Long length variations in the conformation of nucleosomal DNA are identified other than those associated with helix repeat. These variations are required to create a proposed tetrasome conformation or to qualitatively reconstruct the 1.75 turns of the nucleosome's superhelix. Reconstruction of free DNA using selected long wavelength variations in conformation can produce either a left-handed or a right-handed superhelix. The long wavelength variations suggest 146 basepairs is a natural length of DNA to wrap around the histone core. 相似文献
66.
C. N. N′ soukpoé-Kossi C. St-Louis M. Beauregard M. Subirade R. Carpentier S. Hotchandani 《Journal of biomolecular structure & dynamics》2013,31(3):277-283
Abstract Resveratrol (Res), a polyphenolic compound found largely in the skin of red grape and wine, exhibits a wide range of pharmaceutical properties and plays a role in prevention of human cardiovascular diseases [Pendurthi et al., Arterioscler. Thromb. Vasc. Biol. 19, 419–426 (1999)]. It shows a strong affinity towards protein binding and used as inhibitor for cyclo- oxygenase and ribonuclease reductase. The aim of this study was to examine the interaction of resveratrol with human serum albumin (HSA) in aqueous solution at physiological conditions, using a constant protein concentration (0.3 mM) and various pigment contents μM to mM). FTIR, UV-Visible, CD, and fluorescence spectroscopic methods were used to determine the resveratrol binding mode, the binding constant and the effects of pigment complexation on protein secondary structure. Structural analysis showed that resveratrol bind non-specifically (H-bonding) via polypeptide polar groups with overall binding constant of KRes = 2.56× 105 M?1. The protein secondary structure, analysed by CD spectroscopy, showed no major alterations at low resveratrol concentrations (0.125 mM), whereas at high pigment content (1 mM), major increase of α-helix from 57% (free HSA) to 62% and a decrease of β-sheet from 10% (free HSA) to 7% occurred in the resveratrol-HSA complexes. The results indicate a partial stabilization of protein secondary structure at high resveratrol content. 相似文献
67.
Marissa J. Maroni Kimberly M. Capri Alexis V. Cushman Isabella K. Monteiro De Pina Madison H. Chasse 《Chronobiology international》2013,30(10):1456-1463
ABSTRACTDisruptions to the circadian rhythm can lead to altered metabolism. Modification of thyroid function may be a reason why circadian misalignment may contribute to future metabolic disorders. We investigated whether circadian disruption through constant light (LL) can lead to variations in hormone levels associated with thyroid function. Mice were exposed to LL or a 12:12 Light:Dark (LD) cycle for 6 weeks; then glucose tolerance and thyroid hormone levels were measured at ZT 6 and ZT 18. There was day/night variation in glucose tolerance, but LL had no effect. LL reduced TSH, increased fT4, and abolished day/night variation in fT3 and leptin. These findings illustrate that LL alters thyroid-related hormones, providing evidence of a link between circadian disruption and thyroid function. 相似文献
68.
《Chronobiology international》2013,30(5):407-414
This study investigates the possibility of an endogenous circadian rhythm in retinal cone function in humans. A full-field cone electroretinogram (ERG) was performed every 2?h for 24?h under continuous rod-saturating ambient white light (53 ±?30 lux; pupils dilated) in nine healthy subjects. Distinct circadian variations were superimposed upon a gradual decrease in cone responsiveness to light, demonstrated most reliably in the implicit times of b-wave and oscillatory potentials, and to a lesser extent in amplitude and a-wave implicit times. After mathematical correction of the linear trend, the cone response was found to be greatest around 20:00?h and least around 06:00?h. The phase of the ERG circadian rhythm was not synchronized with the phase of the salivary melatonin rhythm measured the previous evening. Melatonin levels measured under constant light on the day of ERG assessments were suppressed by 53% on average compared to melatonin profiles obtained previously under near-total darkness in seven participants. The progressive decline in cone responsiveness to light over the 24?h may reflect an adaptation of the cone-driven retinal system to constant light, although the mechanism is unclear. The endogenous rhythm of cone responsiveness to light may be used as an additional index of central or retinal circadian clock time. (Author correspondence: kvdani@mail. ru) 相似文献
69.
Kathleen A. Burke Karlina J. Kauffman C. Samuel Umbaugh Shelli L. Frey Justin Legleiter 《The Journal of biological chemistry》2013,288(21):14993-15005
Huntington disease (HD) is caused by an expanded polyglutamine (poly(Q)) repeat near the N terminus of the huntingtin (htt) protein. Expanded poly(Q) facilitates formation of htt aggregates, eventually leading to deposition of cytoplasmic and intranuclear inclusion bodies containing htt. Flanking sequences directly adjacent to the poly(Q) domain, such as the first 17 amino acids on the N terminus (Nt17) and the polyproline (poly(P)) domain on the C-terminal side of the poly(Q) domain, heavily influence aggregation. Additionally, htt interacts with a variety of membraneous structures within the cell, and Nt17 is implicated in lipid binding. To investigate the interaction between htt exon1 and lipid membranes, a combination of in situ atomic force microscopy, Langmuir trough techniques, and vesicle permeability assays were used to directly monitor the interaction of a variety of synthetic poly(Q) peptides with different combinations of flanking sequences (KK-Q35-KK, KK-Q35-P10-KK, Nt17-Q35-KK, and Nt17-Q35-P10-KK) on model membranes and surfaces. Each peptide aggregated on mica, predominately forming extended, fibrillar aggregates. In contrast, poly(Q) peptides that lacked the Nt17 domain did not appreciably aggregate on or insert into lipid membranes. Nt17 facilitated the interaction of peptides with lipid surfaces, whereas the poly(P) region enhanced this interaction. The aggregation of Nt17-Q35-P10-KK on the lipid bilayer closely resembled that of a htt exon1 construct containing 35 repeat glutamines. Collectively, this data suggests that the Nt17 domain plays a critical role in htt binding and aggregation on lipid membranes, and this lipid/htt interaction can be further modulated by the presence of the poly(P) domain. 相似文献
70.
Myriam M. Ouberai Juan Wang Marcus J. Swann Celine Galvagnion Tim Guilliams Christopher M. Dobson Mark E. Welland 《The Journal of biological chemistry》2013,288(29):20883-20895
There is increasing evidence for the involvement of lipid membranes in both the functional and pathological properties of α-synuclein (α-Syn). Despite many investigations to characterize the binding of α-Syn to membranes, there is still a lack of understanding of the binding mode linking the properties of lipid membranes to α-Syn insertion into these dynamic structures. Using a combination of an optical biosensing technique and in situ atomic force microscopy, we show that the binding strength of α-Syn is related to the specificity of the lipid environment (the lipid chemistry and steric properties within a bilayer structure) and to the ability of the membranes to accommodate and remodel upon the interaction of α-Syn with lipid membranes. We show that this interaction results in the insertion of α-Syn into the region of the headgroups, inducing a lateral expansion of lipid molecules that can progress to further bilayer remodeling, such as membrane thinning and expansion of lipids out of the membrane plane. We provide new insights into the affinity of α-Syn for lipid packing defects found in vesicles of high curvature and in planar membranes with cone-shaped lipids and suggest a comprehensive model of the interaction between α-Syn and lipid bilayers. The ability of α-Syn to sense lipid packing defects and to remodel membrane structure supports its proposed role in vesicle trafficking. 相似文献