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91.
92.
Nikoleta Karaiskou Maria Lappa Stefanos Kalomoiris George Oikonomidis Chariklia Psaltopoulou Theodore J. Abatzopoulos Costas Triantaphyllidis Alexander Triantafyllidis 《Conservation Genetics》2011,12(5):1299-1311
The ability to detect genetic differences both in space and time is crucial for conserving genetic variation. It can reveal
genetic diversity and genetic composition changes of declining native populations that are supported through stocking with
captive bred individuals. The present study was designed to analyse the temporal stability of a declining common carp (Cyprinus carpio) population from Lake Volvi (North Greece). Polymorphism was evaluated using seven microsatellite loci at two sampling time
points (separated by 12 years). The genetic variability of four additional populations (from two rivers and two lakes) in
Northern Greece was also investigated for comparison. Heterozygosity values (0.692–0.868) and allelic richness (8.530–11.148)
were high for all studied populations and comparable to other European populations. However, the analysis of temporal common
carp samples from Lake Volvi revealed a significant change in their genetic composition and admixture analysis demonstrated
significant introgression of stocked individuals into the native population. Both temporal and point estimate methods revealed
low effective size (Ne = 61–171.3) for this population, possibly a result of an ancient genetic bottleneck that led to population decline and/or
recent anthropogenic interventions. This low Ne has rendered the native population vulnerable to alteration of its genetic composition. Our study demonstrates that enhancement
programs should be applied cautiously, especially for small populations. Moreover, it underlines the need for temporal analyses,
which may contribute to the evaluation of previous management policies and to future decision making. 相似文献
93.
Justin Anglin Reza Beheshti Zavareh Philipp N. Sander Daniel Haldar Edouard Mullarky Lewis C. Cantley Alec C. Kimmelman Costas A. Lyssiotis Luke L. Lairson 《Bioorganic & medicinal chemistry letters》2018,28(16):2675-2678
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is extremely refractory to the therapeutic approaches that have been evaluated to date. Recently, it has been demonstrated that PDAC tumors are dependent upon a metabolic pathway involving aspartate aminotransferase 1, also known as glutamate-oxaloacetate transaminase 1 (GOT1), for the maintenance of redox homeostasis and sustained proliferation. As such, small molecule inhibitors targeting this metabolic pathway may provide a novel therapeutic approach for the treatment of this devastating disease. To this end, from a high throughput screen of ~800,000 molecules, 4-(1H-indol-4-yl)-N-phenylpiperazine-1-carboxamide was identified as an inhibitor of GOT1. Mouse pharmacokinetic studies revealed that potency, rather than inherent metabolic instability, would limit immediate cell- and rodent xenograft-based experiments aimed at validating this potential cancer metabolism-related target. Medicinal chemistry-based optimization resulted in the identification of multiple derivatives with >10-fold improvements in potency, as well as the identification of a tryptamine-based series of GOT1 inhibitors. 相似文献
94.
Makhatadze and Privalov have analyzed the thermodynamics of transfer of aliphatic and aromatic hydrocarbons from the gas phase into water. Finding that the hydration free energy of aliphatic and aromatic hydrocarbons have different signs, they conclude that the mechanism causing hydrophobicity of these solutes is of a different nature. Here, we offer an alternative analysis of the dissolution of these non-polar compounds into water based on a recently published interpretation scheme for thermodynamic transfer functions. Our analysis shows that the hydrophobicity of aromatic and aliphatic hydrocarbons is qualitatively the same, i.e. its causes are the same namely the extremely high cohesive energy of water which overcomes the favorable solute-solute and solute-water interactions. However, both analyses conclude that the experimentally observed quantitative difference between the interactions of water with aliphatic and aromatic hydrocarbons, can be assigned to the formation of aromatic ring-water H-bonds. 相似文献
95.
Dr. Nicole Pasteur Prof. Dr. Costas D. Kastritsis 《Development genes and evolution》1973,173(4):346-354
Summary Alkaline phosphatases and several dehydrogenases and oxidases separated by a microdisc electrophoresis technique have been studied during larval and early pupal development ofD. pseudoobscura salivary glands, fat body, hemolymph, body wall and whole body. Tissue-specific enzymes were observed and the qualitative differences occurring during the development are discussed.This work was supported in part by grants GM-16736-03 and FR-05426-09 from U.S. Department of Health, Education, and Welfare. The work presented is a portion of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy. 相似文献
96.
Adenosine A2A receptors are required for glutamate mGluR5‐ and dopamine D1 receptor‐evoked ERK1/2 phosphorylation in rat hippocampus: involvement of NMDA receptor
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Paraskevi Krania Eleni Dimou Maria Bantouna Stylianos Kouvaros Eirini Tsiamaki Costas Papatheodoropoulos Konstantinos Sarantis Fevronia Angelatou 《Journal of neurochemistry》2018,145(3):217-231
97.
M. M. Fernández Fernández J. A. Pajares Alonso J. M. Salgado Costas 《Journal of Applied Entomology》1999,123(6):321-327
During 1991, 1992, &, 1993 a study on shoot feeding, overwintering and the presence of Tomicus minor inside pine shoots was carried out in the province of León (NW Spain). This paper deals with the duration of these processes, overwintering sites and pine shoot feeding characteristics: age, diameter, length, occurrence of exit holes, multiple attacks and length of the burrowed tunnels. It also refers to the degree of shoot occupation, sex-ratio and detected adult mortality. 相似文献
98.
The effect of specific proline residues on the kinetic stability of the triosephosphate isomerases of two trypanosomes
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Valeria Guzmán‐Luna Andrea G. Quezada A. Jessica Díaz‐Salazar Nallely Cabrera Ruy Pérez‐Montfort Miguel Costas 《Proteins》2017,85(4):571-579
The effect of specific residues on the kinetic stability of two closely related triosephosphate isomerases (from Trypanosoma cruzi, TcTIM and Trypanosoma brucei, TbTIM) has been studied. Based on a comparison of their β‐turn occurrence, we engineered two chimerical enzymes where their super secondary β‐loop‐α motifs 2 ((βα)2) were swapped. Differential scanning calorimetry (DSC) experiments showed that the (βα)2 motif of TcTIM inserted into TbTIM (2Tc) increases the kinetic stability. On the other hand, the presence of the (βα)2 motif of TbTIM inserted into TcTIM (2Tb) gave a chimerical protein difficult to purify in soluble form and with a significantly reduced kinetic stability. The comparison of the contact maps of the (βα)2 of TbTIM and TcTIM showed differences in the contact pattern of residues 43 and 49. In TcTIM these residues are prolines, located at the N‐terminal of loop‐2 and the C‐terminal of α‐helix‐2. Twelve mutants were engineered involving residues 43 and 49 to study the effect over the unfolding activation energy barrier (EA). A systematic analysis of DSC data showed a large decrease on the EA of TcTIM (ΔEA ranging from 468 to 678 kJ/mol) when the single and double proline mutations are present. The relevance of Pro43 to the kinetic stability is also revealed by mutation S43P, which increased the free energy of the transition state of TbTIM by 17.7 kJ/mol. Overall, the results indicate that protein kinetic stability can be severely affected by punctual mutations, disturbing the complex network of interactions that, in concerted action, determine protein stability. Proteins 2017; 85:571–579. © 2016 Wiley Periodicals, Inc. 相似文献
99.
Papaloukas C Granseth E Viklund H Elofsson A 《Protein science : a publication of the Protein Society》2008,17(2):271-278
Zpred2 is an improved version of ZPRED, a predictor for the Z-coordinates of alpha-helical membrane proteins, that is, the distance of the residues from the center of the membrane. Using principal component analysis and a set of neural networks, Zpred2 analyzes data extracted from the amino acid sequence, the predicted topology, and evolutionary profiles. Zpred2 achieves an average accuracy error of 2.18 A (2.17 A when an independent test set is used), an improvement by 15% compared to the previous version. We show that this accuracy is sufficient to enable the predictions of helix lengths with a correlation coefficient of 0.41. As a comparison, two state-of-the-art HMM-based topology prediction methods manage to predict the helix lengths with a correlation coefficient of less than 0.1. In addition, we applied Zpred2 to two other problems, the re-entrant region identification and model validation. Re-entrants were able to be detected with a certain consistency, but not better than with previous approaches, while incorrect models as well as mispredicted helices of transmembrane proteins could be distinguished based on the Z-coordinate predictions. 相似文献
100.
Costas J Carrera N Domínguez E Vilella E Martorell L Valero J Gutiérrez-Zotes A Labad A Carracedo A 《Human genetics》2009,124(6):607-613
The number and frequency of susceptibility alleles at loci associated to most psychiatric disorders is largely unknown, in
spite of its relevance for the design of studies aiming to find these alleles. Both, common polymorphisms and rare mutations
may contribute to the genetic susceptibility to complex psychiatric disorders, being the relative relevance of each type of
variation currently under debate. Here, we confirmed the existence of a common protective haplotype against schizophrenia
at the dopamine D3 receptor (DRD3) gene, by replication and pooled analysis with previous data (Mantel–Haenszel χ2
P value = 0.00227; OR = 0.79, 95% CI 0.68–0.92, based on 794 cases and 1,078 controls from three independent populations of
European origin). This protective haplotype is at very low frequency in Sub-Saharan Africans (median 0.06) and at intermediate
frequencies in other populations (median 0.25). We also revealed, by examining the patterns of linkage disequilibrium around
this gene, that the protective haplotype has reached high frequency in non-African populations due to selection acting, most
probably, on a linked functional polymorphism, the non-synonymous single nucleotide polymorphism Ser9Gly (rs6280), also at
DRD3. Thus, this finding shows that the natural selection may play a role in the existence of common alleles conferring different
susceptibility to schizophrenia.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献