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991.
Bees exposed to vigorous shaking designed to simulate a dangerous event judge ambiguous stimuli as predicting a negative outcome - a 'pessimistic' cognitive bias that is characteristic of anxious or depressed humans and other vertebrates in putative negative emotional states. 相似文献
992.
Eltit JM Feng W Lopez JR Padilla IT Pessah IN Molinski TF Fruen BR Allen PD Perez CF 《The Journal of biological chemistry》2010,285(49):38453-38462
Previously, we have shown that lack of expression of triadins in skeletal muscle cells results in significant increase of myoplasmic resting free Ca(2+) ([Ca(2+)](rest)), suggesting a role for triadins in modulating global intracellular Ca(2+) homeostasis. To understand this mechanism, we study here how triadin alters [Ca(2+)](rest), Ca(2+) release, and Ca(2+) entry pathways using a combination of Ca(2+) microelectrodes, channels reconstituted in bilayer lipid membranes (BLM), Ca(2+), and Mn(2+) imaging analyses of myotubes and RyR1 channels obtained from triadin-null mice. Unlike WT cells, triadin-null myotubes had chronically elevated [Ca(2+)](rest) that was sensitive to inhibition with ryanodine, suggesting that triadin-null cells have increased basal RyR1 activity. Consistently, BLM studies indicate that, unlike WT-RyR1, triadin-null channels more frequently display atypical gating behavior with multiple and stable subconductance states. Accordingly, pulldown analysis and fluorescent FKBP12 binding studies in triadin-null muscles revealed a significant impairment of the FKBP12/RyR1 interaction. Mn(2+) quench rates under resting conditions indicate that triadin-null cells also have higher Ca(2+) entry rates and lower sarcoplasmic reticulum Ca(2+) load than WT cells. Overexpression of FKBP12.6 reverted the null phenotype, reducing resting Ca(2+) entry, recovering sarcoplasmic reticulum Ca(2+) content levels, and restoring near normal [Ca(2+)](rest). Exogenous FKBP12.6 also reduced the RyR1 channel P(o) but did not rescue subconductance behavior. In contrast, FKBP12 neither reduced P(o) nor recovered multiple subconductance gating. These data suggest that elevated [Ca(2+)](rest) in triadin-null myotubes is primarily driven by dysregulated RyR1 channel activity that results in part from impaired FKBP12/RyR1 functional interactions and a secondary increased Ca(2+) entry at rest. 相似文献
993.
Centrosomes comprise a pair of centrioles surrounded by an amorphous network of pericentriolar material (PCM). In certain stem cells, the two centrosomes differ in size, and this appears to be important for asymmetric cell division [1, 2]. In some cases, centrosome asymmetry is linked to centriole age because the older, mother centriole always organizes more PCM than the daughter centriole, thus ensuring that the mother centriole is always retained in the stem cell after cell division [3]. This has raised the possibility that an "immortal" mother centriole may help maintain stem cell fate [4, 5]. It is unclear, however, how centrosome size asymmetry is generated in stem cells. Here we provide compelling evidence that centrosome size asymmetry in Drosophila neuroblasts is generated by the differential regulation of Cnn incorporation into the PCM at mother and daughter centrioles. Shortly after centriole separation, mother and daughter centrioles organize similar amounts of PCM, but Cnn incorporation is then rapidly downregulated at the mother centriole, while it is maintained at the daughter centriole. This ensures that the daughter centriole maintains its PCM and so its position at the apical cortex. Thus, the?daughter centriole, rather than an "immortal" mother centriole, is ultimately retained in these stem cells. 相似文献
994.
Admixture in Mexico City: implications for admixture mapping of Type 2 diabetes genetic risk factors
Martinez-Marignac VL Valladares A Cameron E Chan A Perera A Globus-Goldberg R Wacher N Kumate J McKeigue P O'Donnell D Shriver MD Cruz M Parra EJ 《Human genetics》2007,120(6):807-819
Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases
showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native
American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis
of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275
controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions
were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated
from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and,
West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal
and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent
variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions
was 9.4 (95%, credible interval 3.8–22.6). This association of socioeconomic status with individual admixture proportion shows
that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The
effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7–8.0), from which we can estimate that genome-wide
admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between
populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus
that contributes an ancestry risk ratio of at least 1.5. 相似文献
995.
Nickel tolerance and accumulation by bacteria from rhizosphere of nickel hyperaccumulators in serpentine soil ecosystem of Andaman, India 总被引:1,自引:0,他引:1
Rhizosphere microorganisms harboring nickel hyperaccumulators, Rinorea bengalensis (Wall.) O. K. and Dichapetalum gelonioides ssp. andamanicum (King) Leenh. endemic to serpentine outcrops of Andaman Islands, India, were screened for their tolerance and accumulation
of Ni. The rhizosphere soils from both the plants were rich in total and available Ni along with Co, Cr, Fe and Mg but poor
in microbial density and were dominated by bacteria. Out of total 123 rhizosphere microorganisms (99 bacteria and 24 fungi),
bacteria were more tolerant to Ni than fungi. Viable cells of selected Ni-tolerant bacterial isolates (MIC = 13.6–28.9 mM
Ni) belonging to Pseudomonas, Bacillus and Cupriavidus were capable of accumulating nickel (209.5–224.0 μM Ni g−1 protein) from aqueous solution. Cupriavidus pauculus KPS 201 (MTCC 6280), showing highest degree of nickel tolerance (MIC 28.9 mM Ni) and uptake (224.0 μM Ni g−1 protein, 60 min) was used for detailed study. Kinetics of nickel uptake in C. pauculus KPS 201 followed a linearized Lineweaver-Burk plot. The K
m and V
max for nickel uptake by minimal medium grown-cells approximated 1.5 mM Ni and 636.9 μM Ni g−1 protein, respectively. The uptake process was inhibited by Co, Cu, Cd, Mg, Mn and Zn, however, complete inhibition was not
achieved even in presence of 500 mM Mg. Metabolic inhibitors, sodium azide (1.0 mM) and carbonyl cyanide m-chlorophenylhydrazone (0.4 mM) strongly inhibited nickel uptake suggesting the process as an energy dependent one. The present
study clearly shows that bacteria in the rhizosphere of Ni-hyperaccumulators are capable of tolerating high concentration
of Ni and also possesses nickel uptake potential. The Ni-hyperaccumulators in combination with these Ni-resistant bacteria
could be an ideal tool for nickel bioremediation. 相似文献
996.
Galland N Demeure F Hannaert V Verplaetse E Vertommen D Van der Smissen P Courtoy PJ Michels PA 《Biochimica et biophysica acta》2007,1773(4):521-535
Peroxins 5 and 7 are receptors for protein import into the peroxisomal matrix. We studied the involvement of these peroxins in the biogenesis of glycosomes in the protozoan parasite Trypanosoma brucei. Glycosomes are peroxisome-like organelles in which a major part of the glycolytic pathway is sequestered. We here report the characterization of the T. brucei homologue of PEX7 and provide several data strongly suggesting that it can bind to PEX5. Depletion of PEX5 or PEX7 by RNA interference had a severe effect on the growth of both the bloodstream-form of the parasite, that relies entirely on glycolysis for its ATP supply, and the procyclic form representative of the parasite living in the tsetse-fly midgut and in which also other metabolic pathways play a prominent role. The role of the two receptors in import of glycosomal matrix proteins with different types of peroxisome/glycosome-targeting signals (PTS) was analyzed by immunofluorescence and subcellular fractionation studies. Knocking down the expression of either receptor gene resulted, in procyclic cells, in the mislocalization of proteins with both a type 1 or 2 targeting motif (PTS1, PTS2) located at the C- and N-termini, respectively, and proteins with a sequence-internal signal (I-PTS) to the cytosol. Electron microscopy confirmed the apparent integrity of glycosomes in these procyclic cells. In bloodstream-form trypanosomes, PEX7 depletion seemed to affect only the subcellular distribution of PTS2-proteins. Western blot analysis suggested that, in both life-cycle stages of the trypanosome, the levels of both receptors are controlled in a coordinated fashion, by a mechanism that remains to be determined. The observation that both PEX5 and PEX7 are essential for the viability of the parasite indicates that the respective branches of the glycosome-import pathway in which each receptor acts might be interesting drug targets. 相似文献
997.
LTP inhibits LTD in the hippocampus via regulation of GSK3beta 总被引:2,自引:0,他引:2
Peineau S Taghibiglou C Bradley C Wong TP Liu L Lu J Lo E Wu D Saule E Bouschet T Matthews P Isaac JT Bortolotto ZA Wang YT Collingridge GL 《Neuron》2007,53(5):703-717
Glycogen synthase kinase-3 (GSK3) has been implicated in major neurological disorders, but its role in normal neuronal function is largely unknown. Here we show that GSK3beta mediates an interaction between two major forms of synaptic plasticity in the brain, N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and NMDA receptor-dependent long-term depression (LTD). In rat hippocampal slices, GSK3beta inhibitors block the induction of LTD. Furthermore, the activity of GSK3beta is enhanced during LTD via activation of PP1. Conversely, following the induction of LTP, there is inhibition of GSK3beta activity. This regulation of GSK3beta during LTP involves activation of NMDA receptors and the PI3K-Akt pathway and disrupts the ability of synapses to undergo LTD for up to 1 hr. We conclude that the regulation of GSK3beta activity provides a powerful mechanism to preserve information encoded during LTP from erasure by subsequent LTD, perhaps thereby permitting the initial consolidation of learnt information. 相似文献
998.
999.
DYRK1A enhances the mitogen-activated protein kinase cascade in PC12 cells by forming a complex with Ras, B-Raf, and MEK1 总被引:1,自引:0,他引:1 下载免费PDF全文
Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A) is the human homologue of the Drosophila mnb (minibrain) gene. In Drosophila, mnb is involved in postembryonic neurogenesis. In human, DYRK1A maps within the Down syndrome critical region of chromosome 21 and is overexpressed in Down syndrome embryonic brain. Despite its potential involvement in the neurobiological alterations observed in Down syndrome patients, the biological functions of the serine/threonine kinase DYRK1A have not been identified yet. Here, we report that DYRK1A overexpression potentiates nerve growth factor (NGF)-mediated PC12 neuronal differentiation by up-regulating the Ras/MAP kinase signaling pathway independently of its kinase activity. Furthermore, we show that DYRK1A prolongs the kinetics of ERK activation by interacting with Ras, B-Raf, and MEK1 to facilitate the formation of a Ras/B-Raf/MEK1 multiprotein complex. These data indicate that DYRK1A may play a critical role in Ras-dependent transducing signals that are required for promoting or maintaining neuronal differentiation and suggest that overexpression of DYRK1A may contribute to the neurological abnormalities observed in Down syndrome patients. 相似文献
1000.
Species evolutionary relationships have traditionally been defined by sequence similarities of phylogenetic marker molecules, recently followed by whole-genome phylogenies based on gene order, average ortholog similarity or gene content. Here, we introduce genome conservation--a novel metric of evolutionary distances between species that simultaneously takes into account, both gene content and sequence similarity at the whole-genome level. Genome conservation represents a robust distance measure, as demonstrated by accurate phylogenetic reconstructions. The genome conservation matrix for all presently sequenced organisms exhibits a remarkable ability to define evolutionary relationships across all taxonomic ranges. An assessment of taxonomic ranks with genome conservation shows that certain ranks are inadequately described and raises the possibility for a more precise and quantitative taxonomy in the future. All phylogenetic reconstructions are available at the genome phylogeny server: . 相似文献