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61.
Banach M Prymula K Jurkowski W Konieczny L Roterman I 《Journal of molecular modeling》2012,18(1):229-237
Mutations in proteins introduce structural changes and influence biological activity: the specific effects depend on the location
of the mutation. The simple method proposed in the present paper is based on a two-step model of in silico protein folding.
The structure of the first intermediate is assumed to be determined solely by backbone conformation. The structure of the
second one is assumed to be determined by the presence of a hydrophobic center. The comparable structural analysis of the
set of mutants is performed to identify the mutant-induced structural changes. The changes of the hydrophobic core organization
measured by the divergence entropy allows quantitative comparison estimating the relative structural changes upon mutation.
The set of antifreeze proteins, which appeared to represent the hydrophobic core structure accordant with “fuzzy oil drop”
model was selected for analysis. 相似文献
62.
H5-type influenza virus hemagglutinin is functionally recognized by the natural killer-activating receptor NKp44 总被引:1,自引:0,他引:1
Ho JW Hershkovitz O Peiris M Zilka A Bar-Ilan A Nal B Chu K Kudelko M Kam YW Achdout H Mandelboim M Altmeyer R Mandelboim O Bruzzone R Porgador A 《Journal of virology》2008,82(4):2028-2032
Antiviral immune defenses involve natural killer (NK) cells. We previously showed that the NK-activating receptor NKp44 is involved in the functional recognition of H1-type influenza virus strains by NK cells. In the present study, we investigated the interaction of NKp44 and the hemagglutinin of a primary influenza virus H5N1 isolate. Here we show that recombinant NKp44 recognizes H5-expressing cells and specifically interacts with soluble H5 hemagglutinin. H5-pseudotyped lentiviral particles bind to NK cells expressing NKp44. Following interaction with target cells expressing H5, pseudotyped lentiviral particles, or membrane-associated H5, NK cells show NKp44-mediated induced activity. These findings indicate that NKp44-H5 interactions induce functional NK activation. 相似文献
63.
Peng Y Feng Q Wilk D Adjei AA Salavaggione OE Weinshilboum RM Yee VC 《Biochemistry》2008,47(23):6216-6225
Thiopurine S-methyltransferase (TPMT) modulates the cytotoxic effects of thiopurine prodrugs such as 6-mercaptopurine by methylating them in a reaction using S-adenosyl- l-methionine as the donor. Patients with TPMT variant allozymes exhibit diminished levels of protein and/or enzyme activity and are at risk for thiopurine drug-induced toxicity. We have determined two crystal structures of murine TPMT, as a binary complex with the product S-adenosyl- l-homocysteine and as a ternary complex with S-adenosyl- l-homocysteine and the substrate 6-mercaptopurine, to 1.8 and 2.0 A resolution, respectively. Comparison of the structures reveals that an active site loop becomes ordered upon 6-mercaptopurine binding. The positions of the two ligands are consistent with the expected S N2 reaction mechanism. Arg147 and Arg221, the only polar amino acids near 6-mercaptopurine, are highlighted as possible participants in substrate deprotonation. To probe whether these residues are important for catalysis, point mutants were prepared in the human enzyme. Substitution of Arg152 (Arg147 in murine TPMT) with glutamic acid decreases V max and increases K m for 6-mercaptopurine but not K m for S-adenosyl- l-methionine. Substitution at this position with alanine or histidine and similar substitutions of Arg226 (Arg221 in murine TPMT) result in no effect on enzyme activity. The double mutant Arg152Ala/Arg226Ala exhibits a decreased V max and increased K m for 6-mercaptopurine. These observations suggest that either Arg152 or Arg226 may participate in some fashion in the TPMT reaction, with one residue compensating when the other is altered, and that Arg152 may interact with substrate more directly than Arg226, consistent with observations in the murine TPMT crystal structure. 相似文献
64.
65.
Richard R. Wilk 《Ethnos》2013,78(3-4):294-316
This article discusses two nationalizing projects in the recently independent Caribbean country of Belize. Beauty pageants, promoted by political parties as an explicit effort to build unified national consensus in a multi‐ethnic society, have failed to do so. In practice they dramatize difference more than identity. In the meantime other forms of national identification have flourished, often in sites completely outside of state intervention. An example is provided in the growth of a Belizean cuisine. 相似文献
66.
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68.
Leonie Dengler Nora Kühn Dai-Lun Shin Bastian Hatesuer Klaus Schughart Esther Wilk 《PloS one》2014,9(7)
Influenza A infection is a serious threat to human and animal health. Many of the biological mechanisms of the host-pathogen-interactions are still not well understood and reliable biomarkers indicating the course of the disease are missing. The mouse is a valuable model system enabling us to study the local inflammatory host response and the influence on blood parameters under controlled circumstances. Here, we compared the lung and peripheral changes after PR8 (H1N1) influenza A virus infection in C57BL/6J and DBA/2J mice using virus variants of different pathogenicity resulting in non-lethal and lethal disease. We monitored hematological and immunological parameters revealing that the granulocyte to lymphocyte ratio in the blood represents an early indicator of severe disease progression already two days after influenza A infection in mice. These findings might be relevant to optimize early diagnostic options of severe influenza disease and to monitor successful therapeutic treatment in humans. 相似文献
69.
Piotr Matyjasiak Paweł Boniecki Maciej Fuszara Mateusz Okołowski Izabela Olejniczak 《Animal cells and systems.》2018,22(2):124-131
Feather holes are small (0.5–1?mm in diameter) deformities that appear on the vanes of flight feathers. Such deformities were found in many bird species, including galliforms and passerines. Holey flight feathers may be more permeable to air, which could have a negative effect on their ability to generate aerodynamic forces. However, to date the effects of feather holes on flight performance in birds remained unclear. In this study we investigated the relationship between the number of feather holes occurring in the wing or tail feathers and short term flight performance traits – aerial manoeuvrability, maximum velocity and maximum acceleration – in barns swallows, which are long distance migrating aerial foragers. We measured short-term flight performance of barn swallows in a standardized manner in flight tunnels. We found that acceleration and velocity were significantly negatively associated with the number of holes in the wing flight feathers, but not with those in the tail feathers. In the case of acceleration the negative relationship was sex specific – while acceleration significantly decreased with the number of feather holes in females, there was no such significant association in males. Manoeuvrability was not significantly associated with the number of feather holes. These results are consistent with the hypothesis that feather holes are costly in terms of impaired flight. We discuss alternative scenarios that could explain the observed relationships. We also suggest directions for future studies that could investigate the exact mechanism behind the negative association between the number of feather holes and flight characteristics. 相似文献
70.
Marcin Miłkowski Witold M. Hensel Mateusz Hohol 《Journal of computational neuroscience》2018,45(3):163-172
Replicability and reproducibility of computational models has been somewhat understudied by “the replication movement.” In this paper, we draw on methodological studies into the replicability of psychological experiments and on the mechanistic account of explanation to analyze the functions of model replications and model reproductions in computational neuroscience. We contend that model replicability, or independent researchers' ability to obtain the same output using original code and data, and model reproducibility, or independent researchers' ability to recreate a model without original code, serve different functions and fail for different reasons. This means that measures designed to improve model replicability may not enhance (and, in some cases, may actually damage) model reproducibility. We claim that although both are undesirable, low model reproducibility poses more of a threat to long-term scientific progress than low model replicability. In our opinion, low model reproducibility stems mostly from authors' omitting to provide crucial information in scientific papers and we stress that sharing all computer code and data is not a solution. Reports of computational studies should remain selective and include all and only relevant bits of code. 相似文献