全文获取类型
收费全文 | 4577篇 |
免费 | 239篇 |
国内免费 | 158篇 |
出版年
2024年 | 5篇 |
2023年 | 67篇 |
2022年 | 69篇 |
2021年 | 98篇 |
2020年 | 95篇 |
2019年 | 140篇 |
2018年 | 144篇 |
2017年 | 101篇 |
2016年 | 93篇 |
2015年 | 111篇 |
2014年 | 306篇 |
2013年 | 416篇 |
2012年 | 212篇 |
2011年 | 294篇 |
2010年 | 213篇 |
2009年 | 271篇 |
2008年 | 245篇 |
2007年 | 241篇 |
2006年 | 191篇 |
2005年 | 203篇 |
2004年 | 173篇 |
2003年 | 127篇 |
2002年 | 109篇 |
2001年 | 60篇 |
2000年 | 62篇 |
1999年 | 49篇 |
1998年 | 63篇 |
1997年 | 47篇 |
1996年 | 43篇 |
1995年 | 43篇 |
1994年 | 22篇 |
1993年 | 24篇 |
1992年 | 24篇 |
1991年 | 21篇 |
1990年 | 16篇 |
1989年 | 17篇 |
1988年 | 11篇 |
1987年 | 12篇 |
1986年 | 8篇 |
1985年 | 109篇 |
1984年 | 113篇 |
1983年 | 74篇 |
1982年 | 107篇 |
1981年 | 72篇 |
1980年 | 20篇 |
1979年 | 11篇 |
1978年 | 8篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 3篇 |
排序方式: 共有4974条查询结果,搜索用时 312 毫秒
11.
Rafael L. X. Consani Mariana R. Carmignani Marcelo F. Mesquita Lourenço Correr‐Sobrinho Ricardo D. Guiraldo 《Gerodontology》2010,27(3):236-242
doi:10.1111/j.1741‐2358.2009.00333.x Effect of microwave treatment on the shear bond strength of different types of commercial teeth to acrylic resin Objective: The purpose of this study was to verify the effect of microwave treatment on the shear bond strength of commercial types of teeth to acrylic resin, when the glossy ridge laps were unmodified (groups 1 and 5), bur abraded (groups 2 and 6), bur grooved (groups 3 and 7) or etched by monomer (groups 4 and 8). Background: Controversial findings have shown that mechanical or chemical changes in ridge‐lap surface of the tooth increase or decrease the bond strength between tooth and acrylic resin, and the microwave disinfection may cause different changes on this bond strength. Materials and methods: Eighty specimens (n = 10) were made with the acrylic resin bonded to tooth glossy ridge lap, polymerised in water at 74°C for 9 h, and deflasked after flask cooling. Specimens of the groups 5, 6, 7 and 8 were individually immersed in 150 ml of water and submitted to microwave treatment in an oven at 650 W for 3 min. Control specimens (groups 1, 2, 3 and 4) were not microwave treated. Shear bond strength test was performed in an Instron machine with a cross‐speed of 1 mm/min. Collected data were submitted to anova and Tukey’s test (α = 0.05). Results: Microwave treatment decreased the shear bond strength values of the tooth/resin bond. In the microwaved and non‐microwaved procedures, mechanical retention improved the shear bond strength when compared with the control and monomer treatments. Conclusion: Shear bond strength of the tooth/resin bond was influenced by the microwave treatment and different commercial teeth association, and was lower for the Biotone tooth. 相似文献
12.
Stephen J. Traphagen Michael J. Dimarco Margaret E. Silliker 《RNA (New York, N.Y.)》2010,16(4):828-838
Regions of the Didymium iridis mitochondrial genome were identified with similarity to typical mitochondrial genes; however, these regions contained numerous stop codons. We used RT-PCR and DNA sequencing to determine whether, through RNA editing, these regions were transcribed into mRNAs that could encode functional proteins. Ten putative gene regions were examined: atp1, atp6, atp8, atp9, cox1, cox2, cytb, nad4L, nad6, and nad7. The cDNA sequences of each gene could encode a functional mitochondrial protein that was highly conserved compared with homologous genes. The type of editing events and editing sequence features were very similar to those observed in the homologous genes of Physarum polycephalum, though the actual editing locations showed a variable degree of conservation. Edited sites were compared with encoded sites in D. iridis and P. polycephalum for all 10 genes. Edited sequence for a portion of the cox1 gene was available for six myxomycetes, which, when compared, showed a high degree of conservation at the protein level. Different types of editing events showed varying degrees of site conservation with C-to-U base changes being the least conserved. Several aspects of single C insertion editing events led to the preferential creation of hydrophobic amino acid codons that may help to minimize adverse effects on the resulting protein structure. 相似文献
13.
Yao Chen Jie Zhu Jun Mo Hongyu Yang Xueyang Jiang Hongzhi Lin 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):290-302
Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer’s disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure–activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50?=?10.2?±?1.2, 16.5?±?1.7, and 15.3?±?1.8?nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD. 相似文献
14.
15.
16.
A computer algorithm, CLIX, capable of searching a crystallographic data-base of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three-dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenza-virus hemagglutinin and of proposing a number of potential new ligands to this protein. 相似文献
17.
A. De Marco A. M. Petros R. A. Laursen M. Llinás 《European biophysics journal : EBJ》1987,14(6):359-368
The interaction of the isolated human plasminogen kringle 4 with the four -amino acid ligands -aminocaproic acid (ACA), N-acetyl-l-lysine (AcLys), trans-aminomethyl(cyclohexane)carboxylic acid (AMCHA) and p-benzylaminesulfonic acid (BASA) has been further characterized by 1H-NMR spectroscopy at 300 and 600 MHz. Pronounced high-field shifts, reaching 3 ppm, are observed for AMCHA resonances upon binding to kringle 4, which underscores the relevance of ligand lipophilic interactions with aromatic side chains at the binding site. Ligand titration curves for the nine His and Trp singlets found in the kringle 4 aromatic spectrum reveal a striking uniformity in the kringle response to the various ligands. The average binding curves exhibit a clear Langmuir absorption isotherm saturation profile and the data were analyzed under the assumption of one (high affinity) binding site per kringle. Equilibrium association constants (K
a
) and first order dissociation rate constants (k
off) were derived from linearized expressions of the Langmuir isotherm and of the spectral line-shapes, respectively. The results for the four ligands, at 295 K, pH* 7.2, indicate that: (a) AMCHA exhibits the strongest binding (K
a
=159 mM
-1) and ACA the weakest (K
a
=21 mM
–1) with AcLys and BASA falling in between; (b) ACA dissociates readily (k
off = 5.3 × 103 s–1) and AMCHA associates the fastest (k
off = 2.0 × 108
M
–1 s–1) while the kinetics for BASA exchange is relatively slow (k
off = 0.8 × 103 s–1, k
on = 0.6 × 108
M
–1s–1); (c) the ligand-binding kinetics is close to diffussion-controlled.Abbreviations ACA
-aminocaproic acid
- AcLys
N-acetyl-l-lysine
- AMCHA
t-aminomethyl(cyclohexane)carboxylic acid
- BASA
p-benzylaminesulfonic acid
- K4
kringle 4
- NOE
nuclear Overhauser effect
- ppm
parts-per-million
- pH*
glass electrode pH reading uncorrected for deuterium isotope effects
-
K
a
ligand-kringle 4 equilibrium association constant
-
k
off
ligand-kringle 4 dissociation rate constant
-
k
on
ligand-kringle 4 association rate constant 相似文献
18.
Summary Sequence divergence between the 3 long terminal repeats (LTR) of avian reticuloendotheliosis virus (REV), deletion variant proviral clone 2-20-4, and spleen necrosis virus (SNV)—proviral clones 14-44, 60, and 70—was found to involve two classes of base substitutions: low-frequency interspersed and high-frequency clustered substitutions. Clones 2-20-4 and 14-44 have diverged 4.4% owing to low-frequency substitutions. In contrast, two high-frequency substitution segments have diverged by 30% and 29%, respectively. Clustered substitutions appear to be located either within or next to tandem repeats, suggesting their introduction concomitant with sequence deletions and duplications commonly associated with such repeats. A new 19-bp tandem repeat is found in clone 2-20-4. Its sequence could have evolved from the 26-bp repeats found in the SNV clones. 相似文献
19.
Kenneth A. Marx Ray Kruger Michael J. Clarke 《Molecular and cellular biochemistry》1989,86(2):155-162
The goal of this study is to establish the nature of pentammineruthenium(III) binding to DNA in intact mouse liver nuclei. Also, we wish to determine whether the nucleosomal organization of mouse chromatin has a substantial effect on the relative Ru(III) binding levels of internucleosomal and nucleosomal core DNA. These questions are important because ammineruthenium compounds share chemical and biological properties with the cis-dichlorodiammineplatinum(II) or cisplatin chemotherapeutic agent. Therefore, they represent a potential class of new chemotherapeutic agents. We find that in intact nuclei the predominant DNA binding site for pentammineruthenium(II), followed by air oxidation to pentammineruthenium(III), is N-7 guanine, as is the case with cisplatin. Also, the Ru(III) distribution between internucleosomal and nucleosomal core DNA was found to be nearly identical as probed with three non-specific deoxyribonucleases. 相似文献
20.
Peter Mitchell 《Bioscience reports》1991,11(6):297-346
Chemical transformations, like osmotic translocations, are transport processes when looked at in detail. In chemiosmotic systems, the pathways of specific ligand conduction are spatially orientated through osmoenzymes and porters in which the actions of chemical group, electron and solute transfer occur as vectorial (or higher tensorial order) diffusion processes down gradients of total potential energy that represent real spatially-directed fields of force. Thus, it has been possible to describe classical bag-of-enzymes biochemistry as well as membrane biochemistry in terms of transport. But it would not have been possible to explain biological transport in terms of classical transformational biochemistry or chemistry. The recognition of this conceptual asymmetry in favour of transport has seemed to be upsetting to some biochemists and chemists; and they have resisted the shift towards thinking primarily in terms of the vectorial forces and co-linear displacements of ligands in place of their much less informative scalar products that correspond to the conventional scalar energies. Nevertheless, considerable progress has been made in establishing vectorial metabolism and osmochemistry as acceptable biochemical disciplines embracing transport and metabolism, and bioenergetics has been fundamentally transformed as a result. 相似文献