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101.
Intrinsically disordered proteins (IDPs) are abundant in eukaryotic proteomes and preform critical roles in many cellular processes, most often through the association with globular proteins. Despite lacking a stable three‐dimensional structure by themselves, they may acquire a defined conformation upon binding globular targets. The most common type of secondary structure acquired by these binding motifs entails formation of an α‐helix. It has been hypothesized that such disorder‐to‐order transitions are associated with a significant free energy penalty due to IDP folding, which reduces the overall IDP‐target affinity. However, the exact magnitude of IDP folding penalty in α‐helical binding motifs has not been systematically estimated. Here, we report the folding penalty contributions for 30 IDPs undergoing folding‐upon‐binding and find that the average IDP folding penalty is +2.0 kcal/mol and ranges from 0.7 to 3.5 kcal/mol. We observe that the folding penalty scales approximately linearly with the change in IDP helicity upon binding, which provides a simple empirical way to estimate folding penalty. We analyze to what extent do pre‐structuring and target‐bound IDP dynamics (fuzziness) reduce the folding penalty and find that these effects combined, on average, reduce the folding cost by around half. Taken together, the presented analysis provides a quantitative basis for understanding the role of folding penalty in IDP‐target interactions and introduces a method estimate this quantity. Estimation and reduction of IDP folding penalty may prove useful in the rational design of helix‐stabilized inhibitors of IDP‐target interactions.StatementThe α‐helical binding motifs are ubiquitous among the intrinsically disordered proteins (IDPs). Upon binding their targets, they undergo a disorder‐to‐order transition, which is accompanied by a significant folding penalty whose magnitude is generally not known. Here, we use recently developed statistical‐thermodynamic model to estimate the folding penalties for 30 IDPs and clarify the roles of IDP pre‐folding and bound‐state dynamics in reducing the folding penalty. 相似文献
102.
Miloš K. Mil?i? 《Inorganica chimica acta》2006,359(13):4427-4430
The calculations have been done for CH/π interaction with π-system of Ni(II)-acetylacetonato chelate ring. The results show that there is an attractive electrostatic interaction, while dispersion component is a major source of attractive interacting energies. The interaction was compared with CH/π interaction between two benzene rings. The comparison shows that two interactions are quite similar, enabling to estimate the energy of CH/π interaction with π-system of Ni(II)-acetylacetonato chelate ring to be about 10.5 kJ/mol. The results indicate that CH/π interactions of chelate ring in various molecular systems can be as important as CH/π interactions of phenyl ring. 相似文献
103.
Jafar A. Mammadov Wei Chen Ruihua Ren Reetal Pai Wesley Marchione Feyruz Yalçin Hanneke Witsenboer Thomas W. Greene Steven A. Thompson Siva P. Kumpatla 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(3):577-588
The duplicated and the highly repetitive nature of the maize genome has historically impeded the development of true single
nucleotide polymorphism (SNP) markers in this crop. Recent advances in genome complexity reduction methods coupled with sequencing-by-synthesis
technologies permit the implementation of efficient genome-wide SNP discovery in maize. In this study, we have applied Complexity
Reduction of Polymorphic Sequences technology (Keygene N.V., Wageningen, The Netherlands) for the identification of informative
SNPs between two genetically distinct maize inbred lines of North and South American origins. This approach resulted in the
discovery of 1,123 putative SNPs representing low and single copy loci. In silico and experimental (Illumina GoldenGate (GG)
assay) validation of putative SNPs resulted in mapping of 604 markers, out of which 188 SNPs represented 43 haplotype blocks
distributed across all ten chromosomes. We have determined and clearly stated a specific combination of stringent criteria
(>0.3 minor allele frequency, >0.8 GenTrainScore and >0.5 Chi_test100 score) necessary for the identification of highly polymorphic
and genetically stable SNP markers. Due to these criteria, we identified a subset of 120 high-quality SNP markers to leverage
in GG assay-based marker-assisted selection projects. A total of 32 high-quality SNPs represented 21 haplotypes out of 43
identified in this study. The information on the selection criteria of highly polymorphic SNPs in a complex genome such as
maize and the public availability of these SNP assays will be of great value for the maize molecular genetics and breeding
community. 相似文献
104.
105.
106.
Uchino H Tamai I Yamashita K Minemoto Y Sai Y Yabuuchi H Miyamoto Ki Takeda E Tsuji A 《Biochemical and biophysical research communications》2000,270(1):254-259
Organic anions are secreted into urine via organic anion transporters across the renal basolateral and apical membranes. However, no apical membrane transporter for organic anions such as p-aminohippuric acid (PAH) has yet been identified. In the present study, we showed that human NPT1, which is present in renal apical membrane, mediates the transport of PAH. The K(m) value for PAH uptake was 2.66 mM and the uptake was chloride ion sensitive. These results are compatible with those reported for the classical organic anion transport system at the renal apical membrane. PAH transport was inhibited by various anionic compounds. Human NPT1 also accepted uric acid, benzylpenicillin, faropenem, and estradiol-17beta-glucuronide as substrates. Considering its chloride ion sensitivity, Npt1 is expected to function for secretion of PAH from renal proximal tubular cells. This is the first molecular demonstration of an organic anion transport function for PAH at the renal apical membrane. 相似文献
107.
Bruno Kieffer Patrice Koehl Serge Plaue Jean-François Lefèvre 《Journal of biomolecular NMR》1993,3(1):91-112
Summary We have investigated the dynamics and structural behaviour of two antigenic peptides using 1H NMR. The two cyclic peptides mimic the antigenic site A of influenza haemagglutinin protein; they only differ in the way they were cyclized and in the size of their respective linkers. Homonuclear relaxation parameters extracted from a complete NOE matrix were interpreted in terms of local dynamics. A set of distance constraints was deduced from these parameters which allowed 3D models to be constructed using distance geometry. NOE back-calculation was used to check the validity of the final models. Strong variations of internal motion amplitude have been found in both peptides along their backbone. Motions with high amplitudes have been localized in the Gly-Pro-Gly sequence which forms a -turn in both structures.Abbreviations DSS
3-(trimethylsilyl)-1-propanesulfonic acid
- D-loop
aspartic acid loop
- ELISA
enzyme-linked immunoabsorbent assay
- f.i.d
free induction decay
- HOHAHA
homonuclear Hartmann-Hahn spectroscopy
- HPLC
high pressure liquid chromatography
- K-loop
lysine loop
- NMR
nuclear magnetic resonance
- NOE
nuclear Overhauser enhancement
- NOESY
nuclear Overhauser enhancement spectroscopy
- r.m.s.d.
root-mean-square deviation of atomic positions 相似文献
108.
109.
Isabel C.M. Fensterseifer Mário R. Felício Eliane S.F. Alves Marlon H. Cardoso Marcelo D.T. Torres Carolina O. Matos Osmar N. Silva Timothy K. Lu Maurício V. Freire Natan C. Neves Sónia Gonçalves Luciano M. Lião Nuno C. Santos William F. Porto Cesar de la Fuente-Nunez Octavio L. Franco 《生物化学与生物物理学报:生物膜》2019,1861(7):1375-1387
Infections caused by Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa foremost among them, constitute a major worldwide health problem. Bioinformatics methodologies are being used to rationally design new antimicrobial peptides, a potential alternative for treating these infections. One of the algorithms used to develop antimicrobial peptides is the Joker, which was used to design the peptide PaDBS1R6. This study evaluates the antibacterial activities of PaDBS1R6 in vitro and in vivo, characterizes the peptide interaction to target membranes, and investigates the PaDBS1R6 structure in contact with mimetic vesicles. Moreover, we demonstrate that PaDBS1R6 exhibits selective antimicrobial activity against Gram-negative bacteria. In the presence of negatively charged and zwitterionic lipids the structural arrangement of PaDBS1R6 transits from random coil to α-helix, as characterized by circular dichroism. The tertiary structure of PaDBS1R6 was determined by NMR in zwitterionic dodecylphosphocholine (DPC) micelles. In conclusion, PaDBS1R6 is a candidate for the treatment of nosocomial infections caused by Gram-negative bacteria, as template for producing other antimicrobial agents. 相似文献
110.
Aslı Kurnaz Muazzez Gezelge Aybaba Hançerlioğulları M. Atıf Çetiner Şeref Turhan 《人类与生态风险评估》2016,22(6):1375-1385
The activity concentrations of radionuclides in grape molasses soil samples collected from Zile (Tokat) plain in the Central Black Sea region of Turkey were measured by using gamma spectrometer with a NaI(Tl) detector. Also, the concentrations of 222Rn in soil samples and air were estimated essentially taking the activity concentrations of 226Ra measured in soil samples. Grape molasses soil samples with calcium carbonate content are used for sedimentation for making molasses in this region. The average activity concentrations of 232Th, 226Ra, 40K, and 137Cs were found as 62 ± 2, 68 ± 3, 479 ± 35, and 8.0 ± 0.3 Bq kg?1, respectively. The average concentrations of 222Rn in soil samples and air were estimated to be 50 kBq m?3 and 144 Bq m?3. From the activity concentrations, absorbed gamma dose rate in outdoor air (D), annual effective dose from external exposure (EE), annual effective dose from inhalation of radon (EI), and excess lifetime cancer risk (ELCR) were estimated in order to assess radiological risks. The average values of D, EE, EI, and ELCR were found to be 90 nGy h?1, 110 μSv y?1, 1360 μSv y?1, and 4 × 10?4, respectively. 相似文献