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91.
Ivan Jari Robert J. Lennox Gregor Kalinkat Gor
in Cvijanovi Johannes Radinger 《Global Change Biology》2019,25(2):448-458
Climate change is expected to strongly affect freshwater fish communities. Combined with other anthropogenic drivers, the impacts may alter species spatio‐temporal distributions and contribute to population declines and local extinctions. To provide timely management and conservation of fishes, it is relevant to identify species that will be most impacted by climate change and those that will be resilient. Species traits are considered a promising source of information on characteristics that influence resilience to various environmental conditions and impacts. To this end, we collated life‐history traits and climatic niches of 443 European freshwater fish species and compared those identified as susceptible to climate change to those that are considered to be resilient. Significant differences were observed between the two groups in their distribution, life history, and climatic niche, with climate‐change‐susceptible species being distributed within the Mediterranean region, and being characterized by greater threat levels, lesser commercial relevance, lower vulnerability to fishing, smaller body and range size, and warmer thermal envelopes. Based on our results, we establish a list of species of highest priority for further research and monitoring regarding climate‐change susceptibility within Europe. The presented approach represents a promising tool to efficiently assess large groups of species regarding their susceptibility to climate change and other threats, and to identify research and management priorities. 相似文献
92.
93.
The formation of ecotypes has been invoked as an important driver of postglacial biodiversity, because many species colonized heterogeneous habitats and experienced divergent selection. Ecotype formation has been predominantly studied in outcrossing taxa, while far less attention has been paid to the implications of mating system shifts. Here, we addressed whether substrate‐related ecotypes exist in selfing and outcrossing populations of Arabidopsis lyrata subsp. lyrata and whether the genomic footprint differs between mating systems. The North American subspecies colonized both rocky and sandy habitats during postglacial range expansion and shifted the mating system from predominantly outcrossing to predominantly selfing in a number of regions. We performed an association study on pooled whole‐genome sequence data of 20 selfing or outcrossing populations, which suggested genes involved in adaptation to substrate. Motivated by enriched gene ontology terms, we compared root growth between plants from the two substrates in a common environment and found that plants originating from sand grew roots faster and produced more side roots, independent of mating system. Furthermore, single nucleotide polymorphisms associated with substrate‐related ecotypes were more clustered among selfing populations. Our study provides evidence for substrate‐related ecotypes in A. lyrata and divergence in the genomic footprint between mating systems. The latter is the likely result of selfing populations having experienced divergent selection on larger genomic regions due to higher genome‐wide linkage disequilibrium. 相似文献
94.
Sebastian H. Grimm Berend Gagestein Jordi F. Keijzer Nora Liu Ruud H. Wijdeven Eelke B. Lenselink Adriaan W. Tuin Adrianus M.C.H. van den Nieuwendijk Gerard J.P. van Westen Constant A.A. van Boeckel Herman S. Overkleeft Jacques Neefjes Mario van der Stelt 《Bioorganic & medicinal chemistry》2019,27(5):692-699
Acute myeloid leukemia (AML) is characterized by fast progression and low survival rates, in which Fms-like tyrosine kinase 3 (FLT3) receptor mutations have been identified as a driver mutation in cancer progression in a subgroup of AML patients. Clinical trials have shown emergence of drug resistant mutants, emphasizing the ongoing need for new chemical matter to enable the treatment of this disease. Here, we present the discovery and topological structure-activity relationship (SAR) study of analogs of isoquinolinesulfonamide H-89, a well-known PKA inhibitor, as FLT3 inhibitors. Surprisingly, we found that the SAR was not consistent with the observed binding mode of H-89 in PKA. Matched molecular pair analysis resulted in the identification of highly active sub-nanomolar azaindoles as novel FLT3-inhibitors. Structure based modelling using the FLT3 crystal structure suggested an alternative, flipped binding orientation of the new inhibitors. 相似文献
95.
96.
Eydallin G Morán-Zorzano MT Muñoz FJ Baroja-Fernández E Montero M Alonso-Casajús N Viale AM Pozueta-Romero J 《FEBS letters》2007,581(23):4417-4422
AC70R1-504 Escherichia coli mutants possess a glgC* gene with a nucleotide change resulting in a premature stop codon that renders a truncated, inactive form of GlgC. Cells over-expressing the wild type glgC, but not those over-expressing the AC70R1-504 glgC*, accumulated high ADPglucose and glycogen levels. AC70R1-504 mutants accumulated glycogen, whereas DeltaglgCAP deletion mutants lacking the whole glycogen biosynthetic machinery displayed a glycogen-less phenotype. AC70R1-504 cells with enhanced glycogen synthase activity accumulated high glycogen levels. By contrast, AC70R1-504 cells with high ADPG hydrolase activity accumulated low glycogen. These data further confirm that enterobacteria possess various sources of ADPglucose linked to glycogen biosynthesis. 相似文献
97.
Morán-Zorzano MT Viale AM Muñoz FJ Alonso-Casajús N Eydallín GG Zugasti B Baroja-Fernández E Pozueta-Romero J 《FEBS letters》2007,581(5):1035-1040
Escherichia coli ADP-sugar pyrophosphatase (AspP) is a "Nudix" hydrolase that catalyzes the hydrolytic breakdown of ADP-glucose linked to glycogen biosynthesis. Moderate increases of AspP activity in the cell are accompanied by significant reductions of the glycogen content. In vitro analyses showed that AspP activity is strongly enhanced by macromolecular crowding and by both glucose-1,6-bisphosphate and nucleotide-sugars, providing a first set of indicative evidences that AspP is a highly regulated enzyme. To our knowledge, AspP is the sole bacterial enzyme described to date which is activated by both G1,6P(2) and nucleotide-sugars. 相似文献
98.
The mechanism leading to reinitiation of translation after termination of protein synthesis in eukaryotes has not yet been resolved in detail. One open question concerns the way the post-termination ribosome is tethered to the mRNA to allow binding of the necessary initiation factors. In caliciviruses, a family of positive strand RNA viruses, the capsid protein VP2 is translated via a termination/reinitiation process. VP2 of the feline calicivirus is encoded in the 3'-terminal open reading frame 3 (ORF3) that overlaps with the preceding ORF2 by four nucleotides. In transient expression studies, the efficiency of VP2 expression was 20 times lower than that of the ORF2 proteins. The close vicinity of the ORF2 termination signal and the ORF3 AUG codon was crucial, whereas the AUG could be replaced by alternative codons. Deletion mapping revealed that the 3'-terminal 69 nucleotides of ORF2 are crucial for VP2 expression. This sequence contains two essential sequence motifs. The first motif is conserved among caliciviruses and complementary to part of the 18 S rRNA. In conclusion, VP2 is expressed in a translation termination/reinitiation process that is special because it requires a sequence element that could prevent dissociation of post-termination ribosomes via hybridization with 18 S rRNA. 相似文献
99.
Pauff JM Hemann CF Jünemann N Leimkühler S Hille R 《The Journal of biological chemistry》2007,282(17):12785-12790
The rapid reaction kinetics of wild-type xanthine dehydrogenase from Rhodobacter capsulatus and variants at Arg-310 in the active site have been characterized for a variety of purine substrates. With xanthine as substrate, k(red) (the limiting rate of enzyme reduction by substrate at high [S]) decreased approximately 20-fold in an R310K variant and 2 x 10(4)-fold in an R310M variant. Although Arg-310 lies on the opposite end of the substrate from the C-8 position that becomes hydroxylated, its interaction with substrate still contributed approximately 4.5 kcal/mol toward transition state stabilization. The other purines examined fell into two distinct groups: members of the first were effectively hydroxylated by the wild-type enzyme but were strongly affected by the exchange of Arg-310 to methionine (with a reduction in k(red) greater than 10(3)), whereas members of the second were much less effectively hydroxylated by wild-type enzyme but also much less significantly affected by the amino acid exchanges (with a reduction in k(red) less than 50-fold). The effect was such that the 4000-fold range in k(red) seen with wild-type enzyme was reduced to a mere 4-fold in the R310M variant. The data are consistent with a model in which "good" substrates are bound "correctly" in the active site in an orientation that allows Arg-310 to stabilize the transition state for the first step of the overall reaction via an electrostatic interaction at the C-6 position, thereby accelerating the reaction rate. On the other hand, "poor" substrates bound upside down relative to this "correct" orientation. In so doing, they are unable to avail themselves of the additional catalytic power provided by Arg-310 in wild-type enzyme but, for this reason, are significantly less affected by mutations at this position. The kinetic data thus provide a picture of the specific manner in which the physiological substrate xanthine is oriented in the active site relative to Arg-310 and how this residue is used catalytically to accelerate the reaction rate (rather than simply bind substrate) despite being remote from the position that is hydroxylated. 相似文献
100.
The polypeptides integrating amaranth globulin-p and 11S-globulin were characterized by two-dimensional electrophoresis, ion-exchange
chromatography and RP-HPLC. All polypeptides exhibited charge and hydrophobic heterogeneity. Almost all acid (A, pI 5–7) and
basic (B, pI 9–10) polypeptides were present in both globulins, and the same happened with the unprocessed M polypeptides
with pI in the range of 7–7.5 which fits well with a sequence containing both the A and B polypeptides. There were other polypeptides
only present in 11S-globulin, like some of 41 and 16 kDa, which might come from another precursor or be the products of a
different processing of the propolypeptide. These results suggested that, although amaranth subunits from different subfamilies
are interchangeable in different oligomers, some structural differences between them might affect the assembly of globulin
molecules. Structural differences arising from this behavior could account for the different physicochemical properties of
globulin molecules. 相似文献