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761.
H Inuzuka D Gao LW Finley W Yang L Wan H Fukushima YR Chin B Zhai S Shaik AW Lau Z Wang SP Gygi K Nakayama J Teruya-Feldstein A Toker MC Haigis PP Pandolfi W Wei 《Cell》2012,150(1):179-193
Aberrant Skp2 signaling has been implicated as a driving event in tumorigenesis. Although the underlying molecular mechanisms remain elusive, cytoplasmic Skp2 correlates with more aggressive forms of breast and prostate cancers. Here, we report that Skp2 is acetylated by p300 at K68 and K71, which is a process that can be antagonized by the SIRT3 deacetylase. Inactivation of SIRT3 leads to elevated Skp2 acetylation, which leads to increased Skp2 stability through impairment of the Cdh1-mediated proteolysis pathway. As a result, Skp2 oncogenic function is increased, whereby cells expressing an acetylation-mimetic mutant display enhanced cellular proliferation and tumorigenesis in vivo. Moreover, acetylation of Skp2 in the nuclear localization signal (NLS) promotes its cytoplasmic retention, and cytoplasmic Skp2 enhances cellular migration through ubiquitination and destruction of E-cadherin. Thus, our study identifies an acetylation-dependent regulatory mechanism governing Skp2 oncogenic function and provides insight into how cytoplasmic Skp2 controls cellular migration. 相似文献
762.
Connecting threads: epigenetics and metabolism 总被引:1,自引:0,他引:1
Chromatin-modifying enzymes have long been proposed to be the authors of an epigenetic language, but the origin and meaning of the messages they write in chromatin are still mysterious. Recent studies suggesting that the effects of diet can be passed on epigenetically to offspring add weight to the idea that histones act as metabolic sensors, converting changes in metabolism into stable patterns of gene expression. The challenge will now be to understand how localized fluctuations in levels of metabolites control chromatin modifiers in space and time, translating a dynamic metabolic state into a histone map. 相似文献
763.
764.
765.
Nicla Contran Mariagrazia Tonelli Paolo Crosti Raffaella Cerana Massimo Malerba 《Acta Physiologiae Plantarum》2012,34(2):617-629
Reactive oxygen species (ROS) have pleiotropic effects in plants. ROS can lead to cellular damage and death or play key roles
in control and regulation of biological processes, such as programmed cell death (PCD). This dual role of ROS, as toxic or
signalling molecules, is possible because plant antioxidant system (AS) is able to achieve a tight control over ROS cellular
levels, balancing properly their production and scavenging. AS response in plant PCD has been clearly described only in the
hypersensitive response in incompatible plant–pathogen interactions and in the senescence process and has not been completely
unravelled. In sycamore (Acer pseudoplatanus L.) cultured cells PCD can be induced by Fusicoccin (Fc), Tunicamycin (Tu), and Brefeldin A (Ba). These chemicals induce
comparable PCD time course and extent, while H2O2 production is detectable only in Fc- and, to a lesser extent, in Ba-treated cells. In this paper the AS has been investigated
during PCD of sycamore cells, measuring the effects of the three inducers on the cellular levels of non-enzymatic and enzymatic
antioxidants. Results show that the AS behaviour is different in the PCD induced by the three chemicals. In Fc-treated cells
AS is mainly devoted to decrease the concentration of toxic intracellular H2O2 levels. On the contrary, in cells treated with Tu and Ba, the cell redox state is shifted to a more reduced state and the
enzymatic AS is partially down-regulated, allowing ROS to act as signalling molecules. 相似文献
766.
Cervellati C Montin K Squerzanti M Mischiati C Ferrari C Spinozzi F Mariani P Amenitsch H Bergamini CM Lanzara V 《Amino acids》2012,42(6):2233-2242
Tissue transglutaminase undergoes thermal inactivation with first-order kinetics at moderate temperatures, in a process which is affected in opposite way by the regulatory ligands calcium and GTP, which stabilize different conformations. We have explored the processes of inactivation and of unfolding of transglutaminase and the effects of ligands thereon, combining approaches of differential scanning calorimetry (DSC) and of thermal analysis coupled to fluorescence spectroscopy and small angle scattering. At low temperature (38-45°C), calcium promotes and GTP protects from inactivation, which occurs without detectable disruption of the protein structure but only local perturbations at the active site. Only at higher temperatures (52-56°C), the protein structure undergoes major rearrangements with alterations in the interactions between the N- and C-terminal domain pairs. Experiments by DSC and fluorescence spectroscopy clearly indicate reinforced and weakened interactions of the domains in the presence of GTP and of calcium, and different patterns of unfolding. Small angle scattering experiments confirm different pathways of unfolding, with attainment of limiting values of gyration radius of 52, 60 and 90?? in the absence of ligands and in the presence of GTP and calcium. Data by X-rays scattering indicate that ligands influence retention of a relatively compact structure in the protein even after denaturation at 70°C. These results suggest that the complex regulation of the enzyme by ligands involves both short- and long-range effects which might be relevant for understanding the turnover of the protein in vivo. 相似文献
767.
Siligardi G Ruzza P Hussain R Cesaro L Brunati AM Pinna LA Donella-Deana A 《Amino acids》2012,42(4):1361-1370
HS1 is a protein involved in erythroid proliferation and apoptotic cell death, containing several structurally significant
motifs including a C-terminal SH3 domain. HPK1 is a member of the Ste20-related kinase family, which contains four proline-rich
sequences and is constitutively associated with HS1 in hematopoietic cells. Recombinant fusion protein GST-SH3HS1 was expressed to assess the binding properties of 16 peptides derived from the HPK1 proline-rich regions. The binding affinities
were determined by non-immobilized ligand interaction assay by circular dichroism. Our results revealed that the classical
PxxPxK class II binding motif is not sufficient to induce the interaction with the GST-SH3HS1 domain, an event dependent on the presence of additional basic residue(s) located at the C-terminus of the PxxPxK motif:
Lys−5 in P2 peptide and Lys−8 in P4c peptide. Lys replacement by Arg residues decreases the ligand binding affinity. The finding that both SH3HS1 domain and full-length HS1 protein bind to P2 peptide with similar affinity demonstrates that the whole protein sequence does not affect the interaction properties of
the domain. In silico models of SH3HS1 as a complex with P2 or P4c highlight the domain residues that interact with the recognition determinants of the peptide ligand and that cooperate in
the complex stabilization. 相似文献
768.
Aveta A Tenna S Cagli B Segreto F Lombardo GA Persichetti P 《Plastic and reconstructive surgery》2012,129(6):1004e-1005e; author reply 1005e-1006e
769.
770.
The Miocene Termina Formation of the northern Apennines (Italy) contains thin marly limestone or marly sandstone bodies rich in macrofauna mainly consisting of large lucinid clams. Modern representatives of this fauna occur in cold seep settings where they house chemosymbiotic bacteria. Moreover, these rocks record a δ13C-depletion confirming their origin influenced by a cold seep. The Miocene sections of Sasso delle Streghe and Sarsetta (near Modena) represent classic examples of cold seeps. These sections consist of marls and marly sandstones, respectively, with lucinids (Sasso delle Streghe) or bioclastic sands with lucinids (Sarsetta); both sections are capped by the Sandstones of Montebaranzone. They yield ostracodes that are mainly represented by deep-water filter-feeder species (Platycopa, i.e. Cytherella sp.) and numerous deposit-feeders (Podocopa: i.e. Neonesidea and Krithe), together with species frequently occurring in shallow water environments. These assemblages are able to colonize disaerobic environments such as cold seeps. Although some authors consider the filter-feeders as dominant taxa in disaerobic settings, our data do not provide evidence of significant differences in the ostracode assemblage composition between the deposits originated in seafloors with or without seepage influence. However, the number of specimens is greater in seafloors devoid of seepage influence. 相似文献