全文获取类型
收费全文 | 20934篇 |
免费 | 2098篇 |
国内免费 | 1248篇 |
专业分类
24280篇 |
出版年
2024年 | 72篇 |
2023年 | 446篇 |
2022年 | 510篇 |
2021年 | 724篇 |
2020年 | 812篇 |
2019年 | 1033篇 |
2018年 | 956篇 |
2017年 | 858篇 |
2016年 | 986篇 |
2015年 | 945篇 |
2014年 | 1064篇 |
2013年 | 1971篇 |
2012年 | 953篇 |
2011年 | 917篇 |
2010年 | 804篇 |
2009年 | 1022篇 |
2008年 | 1024篇 |
2007年 | 996篇 |
2006年 | 942篇 |
2005年 | 846篇 |
2004年 | 765篇 |
2003年 | 709篇 |
2002年 | 654篇 |
2001年 | 478篇 |
2000年 | 481篇 |
1999年 | 379篇 |
1998年 | 377篇 |
1997年 | 346篇 |
1996年 | 292篇 |
1995年 | 237篇 |
1994年 | 216篇 |
1993年 | 184篇 |
1992年 | 187篇 |
1991年 | 135篇 |
1990年 | 108篇 |
1989年 | 92篇 |
1988年 | 83篇 |
1987年 | 60篇 |
1986年 | 43篇 |
1985年 | 58篇 |
1984年 | 100篇 |
1983年 | 66篇 |
1982年 | 76篇 |
1981年 | 71篇 |
1980年 | 49篇 |
1979年 | 37篇 |
1978年 | 33篇 |
1977年 | 25篇 |
1976年 | 20篇 |
1973年 | 14篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
941.
942.
Sabra Khorsand Ahmadi Maryam Mahmoodian Moghadam Parisa Mokaberi Mohammad Reza Saberi 《Journal of biomolecular structure & dynamics》2013,31(9):1880-1898
The interaction between bovin β-Lactoglobulin (β-LG) and retinol at two different pH values was investigated by multispectroscopic, zeta potential, molecular modeling, and conductometry measurements. The steady state and polarization fluorescence spectroscopy revealed that complex formation at two different pH values could occur through a remarkable static quenching. According to fluorescence quenching, one set of binding site at pH 2 and two sets of binding sites at pH 7 were introduced for binding of retinol to β-LG that show the enhancement of saturation score of β-LG to retinol in dimmer condition. The polarization fluorescence analysis represented that there is more affinity between β-LG and retinol at pH 7 rather than at pH 2. The effect of retinol on β-LG was studied by UV-visible, circular dichroism (CD), and synchronous fluorescence, which indicated that retinol induced more structural changes on β-LG at pH 7. β-LG–retinol complex formation at two different pH values was recorded via applying resonance light scattering (RLS) and zeta potential. Conductometry and RLS showed two different behaviors of interaction between β-LG and retinol at two different pH values; therefore, dimmer formation played important roles in different behaviors of interaction between β-LG and retinol. The zeta potential was the implied combination of electrostatic and hydrophobic forces which are involved in β-LG–retinol complex at two different pH values, and the hydrophobic interactions play a dominant role in complex formation. Molecular modeling was approved by all experimental results. The acquired results suggested that monomer and dimmer states of β-LG can be induced by retinol with different behaviors. 相似文献
943.
Fangfang Wang Wei Yang Yonghui Shi 《Journal of biomolecular structure & dynamics》2013,31(9):1929-1940
The discovery of clinically relevant inhibitors of retinoic acid receptor-related orphan receptor-gamma-t (RORγt) for autoimmune diseases therapy has proven to be a challenging task. In the present work, to find out the structural features required for the inhibitory activity, we show for the first time a three-dimensional quantitative structure–activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulations for a series of novel thiazole/thiophene ketone amides with inhibitory activity at the RORγt receptor. The optimum CoMFA and CoMSIA models, derived from ligand-based superimposition I, exhibit leave-one-out cross-validated correlation coefficient (R2cv) of .859 and .805, respectively. Furthermore, the external predictive abilities of the models were evaluated by a test set, producing the predicted correlation coefficient (R2pred) of .7317 and .7097, respectively. In addition, molecular docking analysis was applied to explore the binding modes between the inhibitors and the receptor. MD simulation and MM/PBSA method were also employed to study the stability and rationality of the derived conformations, and the binding free energies in detail. The QSAR models and the results of molecular docking, MD simulation, binding free energies corroborate well with each other and further provide insights regarding the development of novel RORγt inhibitors with better activity. 相似文献
944.
Ana Paula Guimarães Teodorico Castro Ramalho 《Journal of biomolecular structure & dynamics》2013,31(10):1601-1612
Smallpox was one of the most devastating diseases in the human history and still represents a serious menace today due to its potential use by bioterrorists. Considering this threat and the non-existence of effective chemotherapy, we propose the enzyme thymidylate kinase from Variola virus (VarTMPK) as a potential target to the drug design against smallpox. We first built a homology model for VarTMPK and performed molecular docking studies on it in order to investigate the interactions with inhibitors of Vaccinia virus TMPK (VacTMPK). Subsequently, molecular dynamics (MD) simulations of these compounds inside VarTMPK and human TMPK (HssTMPK) were carried out in order to select the most promising and selective compounds as leads for the design of potential VarTMPK inhibitors. Results of the docking and MD simulations corroborated to each other, suggesting selectivity towards VarTMPK and, also, a good correlation with the experimental data. 相似文献
945.
《Chronobiology international》2013,30(5):591-595
Performance alterations in executive function have been studied as potential endophenotypes for several neuropsychiatric diseases. Planning is an important component of executive function and has been shown to be affected in diseases such as attention deficit hyperactivity disorder, schizophrenia, obsessive–compulsive disorder and Parkinson’s disease. Several genes related to dopaminergic systems, such as COMT, have been explored as candidates for influencing planning performance. The circadian clock gene PERIOD3 (PER3) has been shown to be associated with several complex behaviors in humans and could be involved in different signaling mechanisms. In this study, we evaluated the possible association between a functional polymorphism in the PER3 gene (PER3-VNTR, rs57875989) and performance in a commonly used test of planning (Tower of London, TOL) in 229 healthy subjects from Bogotá, Colombia. PER3-VNTR genotyping was carried out with conventional PCR and all participants completed the TOL test using the computerized Psychology Experiment Building Language (PEBL) battery. A linear regression model was used for the analysis of association with the SNPStats program. We found that 4/4 genotype carriers showed a better performance and made fewer moves, in comparison to 4/5 and 5/5 genotype carriers (p?=?0.003). These results appear to be independent from effects of this polymorphism on self-reported average hours of sleep during work days in our sample. This is the first evidence of an association between PER3-VNTR and planning performance in a sample of healthy subjects and our results are consistent from previous findings for alterations in other cognitive domains. Future studies examining additional genes could lead to the identification of novel molecular underpinnings of planning in healthy subjects and in patients with neuropsychiatric disorders. 相似文献
946.
The rotavirus genome is composed of 11 gene segments of dsRNA. A recent breakthrough in the field of rotaviruses is the development of a reverse genetics system for generating recombinant rotaviruses possessing a gene segment derived from cloned cDNA. Although this approach is a helper virus‐driven system that is technically limited and gives low levels of recombinant viruses, it allows alteration of the rotavirus genome, thus contributing to our understanding of these medically important viruses. So far, this approach has successfully been applied to three of the 11 viral segments in our laboratory and others, and the efficiency of recovery of recombinant viruses has been improved. However, we are still waiting for the development of a helper virus‐free reverse genetics system for generating an infectious rotavirus entirely from cDNAs, as has been achieved for other members of the Reoviridae family. 相似文献
947.
Abstract Lipid bilayer plays a crucial role in folding of membrane peptides and their stabilization in the membrane-bound state. Correct treatment of the media effects is thus essential for realistic simulations of peptides in bilayers. Previously (Volynsky et al., 1999), we proposed an efficient solvation model which mimics heterogeneous membrane-water system. The model is based on combined employment of atomic solvation parameters for water and hydrocarbon, which approximate hydrated headgroups and acyl chains of lipids, respectively. In this study, the model is employed in non-restrained Monte Carlo simulations of several peptides: totally apolar 20-residue poly-L-Leu, hydrophobic peptide with polar edges, and strongly amphiphilic pep-tide. The principal goals are: to explore energy landscape of these peptides in membrane; to characterize the structures of low-energy states and their orientations with respect to the bilayer. Simulations were performed starting from different structures (unordered or helical) and orientations. It was found that the membrane environment significantly promotes an α-helical conformation for all the peptides, while their energetically favourable orientations are quite different. Thus, poly-Leu was immobilized inside the membrane, the hydrophobic peptide with polar termini adapted transbilayer orientation, whereas the amphiphilic peptide stayed on the lipid-water interface in peripherial orientation. Energy barriers between different states were characterized. The computational results were compared with the experimental structural data. 相似文献
948.
A morphological and molecular examination of the genus Monomorphina was conducted on 46 strains isolated mainly from Korea. The strains were divided into two types based on morphological data: Monomorphina aenigmatica and M. pyrum ‐ like species. Phylogenetic analysis based on a combined data set of nuclear SSU and LSU and plastid SSU and LSU rDNA showed that the strains could be divided into eight clades: Clade A of M. aenigmatica, Clade B of the isolates (M. pyropsis) from Michigan, USA, Clade C of M. pseudopyrum, Clade D of the isolates (M. pyroria) from Bremen, Germany, Clade E of M. soropyrum, Clade F of M. pyriformis, Clade G of M. parapyrum, and Clade H of M. pyrum. Six of these clades came from strains that would be considered M. pyrum sensu Kosmala et Zakry?, one of which could be recognized as a traditional species (M. pyrum) and five were designated as new species; each species had unique molecular signatures at nr SSU rDNA helix 17 and 17′ and spacer E23_14′‐E23_15. The species of Monomorphina had a wide range of genetic diversity with interspecies sequence similarity of 85.6%–97.1% and intraspecies similarity of 96.4%–99.9%. Our results suggested that genetic diversity found in the M. pyrum complex justifies the recognition of a minimum of eight species within this genus, based on specific molecular signatures and gene divergence of the nr SSU rDNA sequences. 相似文献
949.
Oranuch Sanpool Pewpan M. Intapan Tongjit Thanchomnang Penchom Janwan Yukifumi Nawa David Blair Wanchai Maleewong 《The Korean journal of parasitology》2013,51(6):677-681
Paragonimiasis is an important food-borne parasitic zoonosis caused by infection with lung flukes of the genus Paragonimus. Of the 7 members of the genus known in Thailand until recently, only P. heterotremus has been confirmed as causing human disease. An 8th species, P. pseudoheterotremus, has recently been proposed from Thailand, and has been found in humans. Molecular data place this species as a sister species to P. heterotremus, and it is likely that P. pseudoheterotremus is not specifically distinct from P. heterotremus. In this study, we collected metacercariae of both nominal species (identification based on metacercarial morphology) from freshwater crabs from Phetchabun Province in northern Thailand, Saraburi Province in central Thailand, and Surat Thani Province in southern Thailand. In addition, we purchased freshwater crabs imported from Myanmar at Myawaddy Province, western Thailand, close to the Myanmar-Thailand border. The DNAs extracted from excysted metacercariae were PCR-amplified and sequenced for ITS2 and cox1 genes. The ITS2 sequences were nearly identical among all samples (99-100%). Phylogenies inferred from all available partial cox1 sequences contained several clusters. Sequences from Indian P. heterotremus formed a sister group to sequences from P. pseudoheterotremus-type metacercariae. Sequences of P. heterotremus from Thailand, Vietnam, and China formed a separate distinct clade. One metacercaria from Phitsanulok Province was distinct from all others. There is clearly considerable genetic variation in the P. heterotremus complex in Thailand and the form referred to as P. pseudoheterotremus is widely distributed in Thailand and the Thai-Myanmar border region. 相似文献
950.