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971.
Carolina Lúquez Brian H. Raphael Lavin A. Joseph Sarah R. Meno Rafael A. Fernández Susan E. Maslanka 《Applied and environmental microbiology》2012,78(24):8712-8718
Clostridium botulinum type A strains are known to be genetically diverse and widespread throughout the world. Genetic diversity studies have focused mainly on strains harboring one type A botulinum toxin gene, bont/A1, although all reported bont/A gene variants have been associated with botulism cases. Our study provides insight into the genetic diversity of C. botulinum type A strains, which contain bont/A2 (n = 42) and bont/A3 (n = 4) genes, isolated from diverse samples and geographic origins. Genetic diversity was assessed by using bont nucleotide sequencing, content analysis of the bont gene clusters, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Sequences of bont genes obtained in this study showed 99.9 to 100% identity with other bont/A2 or bont/A3 gene sequences available in public databases. The neurotoxin gene clusters of the subtype A2 and A3 strains analyzed in this study were similar in gene content. C. botulinum strains harboring bont/A2 and bont/A3 genes were divided into six and two MLST profiles, respectively. Four groups of strains shared a similarity of at least 95% by PFGE; the largest group included 21 out of 46 strains. The strains analyzed in this study showed relatively limited genetic diversity using either MLST or PFGE. 相似文献
972.
973.
Khomenko T Kolodney J Pinto JT McLaren GD Deng X Chen L Tolstanova G Paunovic B Krasnikov BF Hoa N Cooper AJ Szabo S 《Archives of biochemistry and biophysics》2012,525(1):60-70
Cysteamine, a coenzyme A metabolite, induces duodenal ulcers in rodents. Our recent studies showed that ulcer formation was aggravated by iron overload and diminished in iron deficiency. We hypothesized that cysteamine is selectively taken up in the duodenal mucosa, where iron absorption primarily occurs, and is transported by a carrier-mediated process. Here we report that cysteamine administration in rats leads to cysteamine accumulation in the proximal duodenum, where the highest concentration of iron in the gastrointestinal tract is found. In vitro, iron loading of intestinal epithelial cells (IEC-6) accelerated reactive oxygen species (ROS) production and increased [(14)C]cysteamine uptake. [(14)C]Cysteamine uptake by isolated gastrointestinal mucosal cells and by IEC-6 was pH-dependent and inhibited by unlabeled cysteamine. The uptake of [(14)C]cysteamine by IEC-6 was Na(+)-independent, saturable, inhibited by structural analogs, H(2)-histamine receptor antagonists, and organic cation transporter (OCT) inhibitors. OCT1 mRNA was markedly expressed in the rat duodenum and in IEC-6, and transfection of IEC-6 with OCT1 siRNA decreased OCT1 mRNA expression and inhibited [(14)C]cysteamine uptake. Cysteamine-induced duodenal ulcers were decreased in OCT1/2 knockout mice. These studies provide new insights into the mechanism of cysteamine absorption and demonstrate that intracellular iron plays a critical role in cysteamine uptake and in experimental duodenal ulcerogenesis. 相似文献
974.
Wang Y Pinto JR Solis RS Dweck D Liang J Diaz-Perez Z Ge Y Walker JW Potter JD 《The Journal of biological chemistry》2012,287(3):2156-2167
The R21C substitution in cardiac troponin I (cTnI) is the only identified mutation within its unique N-terminal extension that is associated with hypertrophic cardiomyopathy (HCM) in man. Particularly, this mutation is located in the consensus sequence for β-adrenergic-activated protein kinase A (PKA)-mediated phosphorylation. The mechanisms by which this mutation leads to heart disease are still unclear. Therefore, we generated cTnI knock-in mouse models carrying an R21C mutation to evaluate the resultant functional consequences. Measuring the in vivo levels of incorporated mutant and WT cTnI, and their basal phosphorylation levels by top-down mass spectrometry demonstrated: 1) a dominant-negative effect such that, the R21C+/- hearts incorporated 24.9% of the mutant cTnI within the myofilament; and 2) the R21C mutation abolished the in vivo phosphorylation of Ser(23)/Ser(24) in the mutant cTnI. Adult heterozygous (R21C+/-) and homozygous (R21C+/+) mutant mice activated the fetal gene program and developed a remarkable degree of cardiac hypertrophy and fibrosis. Investigation of cardiac skinned fibers isolated from WT and heterozygous mice revealed that the WT cTnI was completely phosphorylated at Ser(23)/Ser(24) unless the mice were pre-treated with propranolol. After propranolol treatment (-PKA), the pCa-tension relationships of all three mice (i.e. WT, R21C+/-, and R21C+/+) were essentially the same. However, after treatment with propranolol and PKA, the R21C cTnI mutation reduced (R21C+/-) or abolished (R21C+/+) the well known decrease in the Ca(2+) sensitivity of tension that accompanies Ser(23)/Ser(24) cTnI phosphorylation. Altogether, the combined effects of the R21C mutation appear to contribute toward the development of HCM and suggest that another physiological role for the phosphorylation of Ser(23)/Ser(24) in cTnI is to prevent cardiac hypertrophy. 相似文献
975.
Quercus forest regeneration is limited by different factors, post-dispersal predation being one of the most critical stages. We analysed seed removal of four coexisting Quercus species (Q. ilex, Q. suber, Q. faginea and Q. pyrenaica) in a Mediterranean forest located in Southern Spain. Marked and weighed acorns from each of the species were placed in experimental units with or without exclusion of large herbivores and in two microhabitat types (Q. ilex shade or open). Acorn removal was monitored for 120?days in order to test the effect of exclusion of large herbivore and microhabitat type on seed removal rates and species selection. Interestingly, the results of microhabitat and species selection differed depending on the presence of large herbivores. Removal was faster in sites without exclusion, where most seeds (??85%) disappeared during the first 9?days. In these sites, no differences in seed removal were found between different microhabitats, but seeds of two species, those with higher seed mass (Q. suber and Q. pyrenaica) were most preferred. However, under exclusion of large herbivores, seed removal was affected by the microhabitat, this being greater in Q. ilex shaded microhabitats, which showed a higher structural diversity. Also, species selection was completely different under exclusion of large herbivores, and seeds of Q. ilex and Q. faginea were removed faster. These results highlight the importance of large herbivore activity on seed removal and its effect on microhabitat and species selection. Therefore, specific selection by seed consumers may modify seedling recruitment and may have an important influence on the relative abundance of coexisting Quercus species. 相似文献
976.
977.
Tóth R Gerding-Reimers C Deeks MJ Menninger S Gallegos RM Tonaco IA Hübel K Hussey PJ Waldmann H Coupland G 《The Plant journal : for cell and molecular biology》2012,71(2):338-352
Chemical modulators are powerful tools to investigate biological processes. To identify circadian clock effectors, we screened a natural product library in the model plant Arabidopsis thaliana. Two compounds, prieurianin (Pri) and prieurianin acetate, were identified as causing a shorter circadian period. Recently, Pri was independently identified as a vesicle trafficking inhibitor and re-named endosidin 1 (ES1). Here we show that Pri primarily affects actin filament flexibility in vivo, later resulting in reduced severing and filament depolymerization. This stabilization of the actin cytoskeleton subsequently causes changes in vesicle trafficking. Pri also affected microfilaments in mammalian cells, indicating that its target is highly conserved; however, it did not alter actin dynamics in vitro, suggesting that its activity requires the presence of actin-associated proteins. Furthermore, well-characterized actin inhibitors shortened the period length of the Arabidopsis clock in a similar way to Pri, supporting the idea that Pri affects rhythms by altering the actin network. We conclude that actin-associated processes influence the circadian system in a light-dependent manner, but their disruption does not abolish rhythmicity. In summary, we propose that the primary effect of Pri is to stabilize the actin cytoskeleton system, thereby affecting endosome trafficking. Pri appears to stabilize actin filaments by a different mechanism from previously described inhibitors, and will be a useful tool to study actin-related cellular processes. 相似文献
978.
Shen HC Ding FX Jiang J Verras A Chabin RM Xu S Tong X Chen Q Xie D Lassman ME Bhatt UR Garcia-Calvo MM Geissler W Shen Z Murphy BA Gorski JN Wiltsie J SinhaRoy R Hale JJ Pinto S Shen DM 《Bioorganic & medicinal chemistry letters》2012,22(4):1550-1556
A series of benzodihydroisofurans were discovered as novel, potent, bioavailable and brain-penetrant prolylcarboxypeptidase (PrCP) inhibitors. The structure-activity relationship (SAR) is focused on improving PrCP activity and metabolic stability, and reducing plasma protein binding. In the established diet-induced obese (eDIO) mouse model, compound ent-3a displayed target engagement both in plasma and in brain. However, this compound failed to induce significant body weight loss in eDIO mice in a five-day study. 相似文献
979.
Previous epidemiological studies on SIS model have only considered the dynamic evolution of the mean value and the variance of the infected individuals. In this paper, through cumulant neglection, we use the dynamic equations of all the moments of infected individuals to develop a recursive method to compute the equilibria manifold of the moment closure ODE's. Specifically, we use the stable equilibria of the moment closure ODE's to obtain good approximations of the quasi-stationary states of the SIS model. This is a crucial step when the quasi-stationary distribution is highly skewed. 相似文献
980.
Moreno-Pérez AJ Venegas-Calerón M Vaistij FE Salas JJ Larson TR Garcés R Graham IA Martínez-Force E 《Planta》2012,235(3):629-639
Acyl–acyl carrier protein (ACP) thioesterases are enzymes that control the termination of intraplastidial fatty acid synthesis
by hydrolyzing the acyl–ACP complexes. Among the different thioesterase gene families found in plants, the FatA-type fulfills a fundamental role in the export of the C18 fatty acid moieties that will be used to synthesize most plant
glycerolipids. A reverse genomic approach has been used to study the FatA thioesterase in seed oil accumulation by screening
different mutant collections of Arabidopsis thaliana for FatA knockouts. Two mutants were identified with T-DNA insertions in the promoter region of each of the two copies of FatA present in the Arabidopsis genome, from which a double FatA Arabidopsis mutant was made. The expression of both forms of FatA thioesterases was reduced in this double mutant (fata1 fata2), as was FatA activity. This decrease did not cause any evident morphological changes in the mutant plants, although the partial
reduction of this activity affected the oil content and fatty acid composition of the Arabidopsis seeds. Thus, dry mutant
seeds had less triacylglycerol content, while other neutral lipids like diacylglycerols were not affected. Furthermore, the
metabolic flow of the different glycerolipid species into seed oil in the developing seeds was reduced at different stages
of seed formation in the fata1 fata2 line. This diminished metabolic flow induced increases in the proportion of linolenic and erucic fatty acids in the seed
oil, in a similar way as previously reported for the wri1 Arabidopsis mutant that accumulates oil poorly. The similarities between these two mutants and the origin of their phenotype
are discussed in function of the results. 相似文献