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901.
Drp1 mediates caspase-independent type III cell death in normal and leukemic cells 总被引:4,自引:0,他引:4
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Bras M Yuste VJ Roué G Barbier S Sancho P Virely C Rubio M Baudet S Esquerda JE Merle-Béral H Sarfati M Susin SA 《Molecular and cellular biology》2007,27(20):7073-7088
Ligation of CD47 triggers caspase-independent programmed cell death (PCD) in normal and leukemic cells. Here, we characterize the morphological and biochemical features of this type of death and show that it displays the hallmarks of type III PCD. A molecular and biochemical approach has led us to identify a key mediator of this type of death, dynamin-related protein 1 (Drp1). CD47 ligation induces Drp1 translocation from cytosol to mitochondria, a process controlled by chymotrypsin-like serine proteases. Once in mitochondria, Drp1 provokes an impairment of the mitochondrial electron transport chain, which results in dissipation of mitochondrial transmembrane potential, reactive oxygen species generation, and a drop in ATP levels. Surprisingly, neither the activation of the most representative proapoptotic members of the Bcl-2 family, such as Bax or Bak, nor the release of apoptogenic proteins AIF (apoptosis-inducing factor), cytochrome c, endonuclease G (EndoG), Omi/HtrA2, or Smac/DIABLO from mitochondria to cytosol is observed. Responsiveness of cells to CD47 ligation increases following Drp1 overexpression, while Drp1 downregulation confers resistance to CD47-mediated death. Importantly, in B-cell chronic lymphocytic leukemia cells, mRNA levels of Drp1 strongly correlate with death sensitivity. Thus, this previously unknown mechanism controlling caspase-independent type III PCD may provide the basis for novel therapeutic approaches to overcome apoptotic avoidance in malignant cells. 相似文献
902.
Identifying prosurvival mechanisms in stressed neuronal cells would provide protective strategies to hinder neurodegeneration.
Recent evidence shows that vascular endothelial growth factor (VEGF), a well-established mitogen in endothelial cells, can
mediate neuroprotection against damaging insults through the activation of its cognate receptor VEGFR2. In addition, growth
factor receptor signaling pathways have been shown to crosstalk with cAMP-dependent Protein Kinase A (PKA) to protect neuronal
cells from harmful stimuli. Whether a relationship exists between VEGFR2 and PKA in mediating neuroprotection under stressful
conditions is unknown. Using SK-N-SH neuronal cells as a model system, we show that serum deprivation induces an upregulation
in VEGF and VEGFR2 that concomitantly serves as a prosurvival signaling pathway. Inhibitor studies revealed that PKA functioned
concurrently with VEGFR2 pathway to signal the activation of the extracellular signal-regulated protein kinases (ERK1/2) as
protection against caspase-3/7 activation and a subsequent cell death. The loss in cell viability induced by VEGFR2 and PKA
inhibition was prevented by caspase inhibition or overexpression of ERK1. Overexpression of the antiapoptotic protein Bcl-xL
also promoted survival when VEGFR2 function was blocked. However, the protection elicited by all three treatments were prevented
by the inclusion of a selective inhibitor of mitogen-activated protein kinase kinase (MEK), the upstream kinase that activates
ERK1/2. Taken together, these findings suggested that PKA and VEGFR2 converge at the MEK/ERK1/2 pathway to protect serum starved
neuronal cells from a caspase-dependent cell death.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
903.
Neves FO Abreu PA Vasconcellos SA de Morais ZM Romero EC Nascimento AL 《Archives of microbiology》2007,188(5):523-532
This study examined four genes encoding for predicted membrane proteins selected from the genome sequences of Leptospira interrogans. Genes were cloned and the proteins expressed in E. coli. Immunoblotting analysis of the recombinants with sera from early and convalescent phases of a leptospirosis patient showed
that two proteins, namely Lp29 and Lp49, were reactive with serum from both phases of the illness. These data were further
confirmed in enzyme-linked immunosorbent assay using sera from both phases of seventeen confirmed leptospirosis specimens,
suggesting that these proteins are presented to the host immune system during infection. In the early phase, anti-Lp29 IgM
was detected in all sera when microscopic agglutination tests (MAT), the reference method for diagnosis of leptospirosis,
were negative. The gene encoding Lp49 is conserved among five tested leptospiral pathogenic serovars, while Lp29 is present
in serovars that are predominant in urban settings. These recombinant antigens might be valuable for serodiagnosis of both
phases of leptospirosis. 相似文献
904.
905.
Patricia S. Santiago Leonardo M. MoreiraErika V. de Almeida Marcel Tabak 《Biochimica et Biophysica Acta (BBA)/General Subjects》2007
The effects of two ionic surfactants on the oligomeric structure of the giant extracellular hemoglobin of Glossoscolex paulistus (HbGp) in the oxy - form have been studied through the use of several spectroscopic techniques such as electronic optical absorption, fluorescence emission, light scattering, and circular dichroism. The use of anionic sodium dodecyl sulphate (SDS) and cationic cethyltrimethyl ammonium chloride (CTAC) has allowed to differentiate the effects of opposite headgroup charges on the oligomeric structure dissociation and hemoglobin autoxidation. At pH 7.0, both surfactants induce the protein dissociation and a significant oxidation. Spectral changes occur at very low CTAC concentrations suggesting a significant electrostatic contribution to the protein–surfactant interaction. At low protein concentration, 0.08 mg/ml, some light scattering within a narrow CTAC concentration range occurs due to protein–surfactant precipitation. Light scattering experiments showed the dissociation of the oligomeric structure by SDS and CTAC, and the effect of precipitation induced by CTAC. At higher protein concentrations, 3.0 mg/ml, a precipitation was observed due to the intense charge neutralization upon formation of ion pair in the protein–surfactant precipitate. The spectral changes are spread over a much wider SDS concentration range, implying a smaller electrostatic contribution to the protein–surfactant interactions. The observed effects are consistent with the acid isoelectric point (pI) of this class of hemoglobins, which favors the intense interaction of HbGp with the cationic surfactant due to the existence of excess acid anionic residues at the protein surface. Protein secondary structure changes are significant for CTAC at low concentrations while they occur at significantly higher concentrations for SDS. In summary, the cationic surfactant seems to interact more strongly with the protein producing more dramatic spectral changes as compared to the anionic one. This is opposite as observed for several other hemoproteins. The surfactants at low concentrations produce the oligomeric dissociation, which facilitates the iron oxidation, an important factor modulating further oligomeric protein dissociation. 相似文献
906.
907.
908.
909.
Campylobacter insulaenigrae Isolates from Northern Elephant Seals (Mirounga angustirostris) in California
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Robyn A. Stoddard William G. Miller Janet E. Foley Judy Lawrence Frances M. D. Gulland Patricia A. Conrad Barbara A. Byrne 《Applied microbiology》2007,73(6):1729-1735
There are only two reports in the literature demonstrating the presence of Campylobacter spp. in marine mammals. One report describes the isolation of a new species, Campylobacter insulaenigrae sp. nov., from three harbor seals (Phoca vitulina) and a harbor porpoise (Phocoena phocoena) in Scotland, and the other describes the isolation of Campylobacter jejuni, Campylobacter lari, and an unknown Campylobacter species from northern elephant seals (Mirounga angustirostris) in California. In this study, 72 presumptive C. lari and unknown Campylobacter species strains were characterized using standard phenotypic methods, 16S rRNA PCR, and multilocus sequence typing (MLST). Phenotypic characterization of these isolates showed them to be variable in their ability to grow either at 42°C or on agar containing 1% glycine and in their sensitivity to nalidixic acid and cephalothin. Based on both 16S rRNA PCR and MLST, all but 1 of the 72 isolates were C. insulaenigrae, with one isolate being similar to but distinct from both Campylobacter upsaliensis and Campylobacter helveticus. Phylogenetic analysis identified two C. insulaenigrae clades: the primary clade, containing exclusively California strains, and a secondary clade, containing some California strains and all of the original Scottish strains. This study demonstrates the inability of phenotypic characterization to correctly identify all Campylobacter species and emphasizes the importance of molecular characterization via 16S rRNA sequence analysis or MLST for the identification of Campylobacter isolates from marine mammals. 相似文献
910.
Susan E. Gresens Kenneth T. Belt Jamie A. Tang Daniel C. Gwinn Patricia A. Banks 《Hydrobiologia》2007,575(1):173-190
In a longitudinal study of two streams whose lower reaches received unattenuated urban stormwater runoff, physical disturbance
by stormflow was less important than the persistant unidentified chemical impacts of urban stormwater in limiting the distribution
of Chironomidae, and Ephemeroptera, Trichoptera and Plecoptera (EPT). A hierarchical spatial analysis showed that chironomid
density did not decrease from rural to urban stream reaches. Instead, the taxonomic composition of chironomid assemblages
was significantly altered in urban versus rural reaches; chironomid assemblages in urban reaches exhibited higher average
pollution tolerance scores. In contrast, the density of EPT was significantly lower in urban reaches. Despite higher values
of stormflow tractive force in urban reaches, streambed stability tended to be greater in urban reaches. Modeling of temporal
variation in chironomid density showed similar patterns in both rural and urban reaches: chironomid density had a unimodal
relationship to rainfall index (RI), with highest densities at intermediate values of RI. Models of EPT density over time
in rural reaches showed no significant relation to RI, and temporal variation in EPT density in urban reaches was not predictable.
The abundance of fine particulate organic matter, including periphyton (FPOM), on cobbles was greater in urban reaches and
showed a much greater degree of temporal variation than in rural reaches. In urban reaches, a negative relation between FPOM
and RI indicated the importance of stormflow abrasion.
Handling editor: K. Martens 相似文献