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991.
The expression of alpha-subunit of interleukin-2 receptor (IL-2Ralpha) was assessed by quantifying activation-induced upregulation of CD25 in human blood lymphocytes (HBL) stimulated by interleukin-2 (IL-2). It was established that exogenous IL-2 induced no surface expression of CD25 neither proliferation at 48 h of IL-2 action. In component HBL, pretreated by sub-mitogenic doses of phytohemagglutinin (PHA), 5-15 % of cell population was revealed to represent the CD2t+ cells, and in the competent cells only, exogenous IL-2 induced the surface expression of CD25 as well as the growth and the proliferative response, which was comparable with those to mitogenic doses of PHA. The JAK3 inhibitor WHI-P131 eliminated IL-2-dependent CD25 expression without influencing the CD25 expression in competent cells. Unlike, PP2 was found to inhibit the IL-2-dependent CD25 expression in a lesser extent than WHI-P131, however this drug was effectively inhibited CD25 expression in PHA-pretreated, competent HBL. These data suggest that Src-dependent signaling participate in the early IL-2Ralpha expression that precedes the IL-2-dependent cell cycle progression of activated HBL. It is concluded that in normal T cells, the IL-2Ralpha expression in firstly induced by antigen (mitogen) and thereafter it is held IL-2 through JAK-dependent signaling pathway. 相似文献
992.
Soldner F Laganière J Cheng AW Hockemeyer D Gao Q Alagappan R Khurana V Golbe LI Myers RH Lindquist S Zhang L Guschin D Fong LK Vu BJ Meng X Urnov FD Rebar EJ Gregory PD Zhang HS Jaenisch R 《Cell》2011,146(2):318-331
Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease, as well as a promising source for cell replacement therapies. One crucial limitation has been the inability to perform experiments under genetically defined conditions. This is particularly relevant for late age onset disorders in which in vitro phenotypes are predicted to be subtle and susceptible to significant effects of genetic background variations. By combining zinc finger nuclease (ZFN)-mediated genome editing and iPSC technology, we provide a generally applicable solution to this problem, generating sets of isogenic disease and control human pluripotent stem cells that differ exclusively at either of two susceptibility variants for Parkinson's disease by modifying the underlying point mutations in the α-synuclein gene. The robust capability to genetically correct disease-causing point mutations in patient-derived hiPSCs represents significant progress for basic biomedical research and an advance toward hiPSC-based cell replacement therapies. 相似文献
993.
Ojovan SM Knorre DA Markova OV Smirnova EA Bakeeva LE Severin FF 《Journal of bioenergetics and biomembranes》2011,43(2):175-180
Hydrophobic cations with delocalized charge are used to deliver drugs to mitochondria. However, micromolar concentrations
of such compounds could be toxic due to their excessive accumulation in mitochondria. We studied possible pathophysiological
effects of one such cation, i.e. dodecyltriphenylphosphonium (C12-TPP), in the yeast Saccharomyces cerevisiae. First, we found that C12-TPP induces high-amplitude mitochondrial swelling. The swelling can be prevented by addition of protonophorous uncoupler
FCCP or antioxidant alpha-tocopherol, but not other tested antioxidants (N-acetylcysteine and Trolox). Second, FCCP prevents
ROS-sensitive fluorescent dye (dichlorofluorescein diacetate) staining of yeast treated with C12-TPP. We also showed that all tested antioxidants partially restore the growth inhibited by C12-TPP. The latter points that ROS rather than the mitochondria swelling limit the growth rate. 相似文献
994.
Ghilarov D Serebryakova M Shkundina I Severinov K 《The Journal of biological chemistry》2011,286(30):26308-26318
Microcin B17 (McB) is a 43-amino acid antibacterial peptide targeting the DNA gyrase. The McB precursor is ribosomally produced and then post-translationally modified by the McbBCD synthase. Active mature McB contains eight oxazole and thiazole heterocycles. Here, we show that a major portion of mature McB contains an additional unusual modification, a backbone ester bond connecting McB residues 51 and 52. The modification results from an N → O shift of the Ser(52) residue located immediately downstream of one of McB thiazole heterocycles. We speculate that the N,O-peptidyl shift undergone by Ser(52) is an intermediate of post-translational modification reactions catalyzed by the McbBCD synthase that normally lead to formation of McB heterocycles. 相似文献
995.
996.
Kirpota OO Endutkin AV Ponomarenko MP Ponomarenko PM Zharkov DO Nevinsky GA 《Nucleic acids research》2011,39(11):4836-4850
We have used a stepwise increase in ligand complexity approach to estimate the relative contributions of the nucleotide units of DNA containing 7,8-dihydro-8-oxoguanine (oxoG) to its total affinity for human 8-oxoguanine DNA glycosylase (OGG1) and construct thermodynamic models of the enzyme interaction with cognate and non-cognate DNA. Non-specific OGG1 interactions with 10–13 nt pairs within its DNA-binding cleft provides approximately 5 orders of magnitude of its affinity for DNA (ΔG° approximately −6.7 kcal/mol). The relative contribution of the oxoG unit of DNA (ΔG° approximately −3.3 kcal/mol) together with other specific interactions (ΔG° approximately −0.7 kcal/mol) provide approximately 3 orders of magnitude of the affinity. Formation of the Michaelis complex of OGG1 with the cognate DNA cannot account for the major part of the enzyme specificity, which lies in the kcat term instead; the rate increases by 6–7 orders of magnitude for cognate DNA as compared with non-cognate one. The kcat values for substrates of different sequences correlate with the DNA twist, while the KM values correlate with ΔG° of the DNA fragments surrounding the lesion (position from −6 to +6). The functions for predicting the KM and kcat values for different sequences containing oxoG were found. 相似文献
997.
998.
999.
Zhao N Pang B Shyu CR Korkin D 《Protein science : a publication of the Protein Society》2011,20(7):1275-1284
Protein-protein interactions play an essential role in the functioning of cell. The importance of charged residues and their diverse role in protein-protein interactions have been well studied using experimental and computational methods. Often, charged residues located in protein interaction interfaces are conserved across the families of homologous proteins and protein complexes. However, on a large scale, it has been recently shown that charged residues are significantly less conserved than other residue types in protein interaction interfaces. The goal of this work is to understand the role of charged residues in the protein interaction interfaces through their conservation patterns. Here, we propose a simple approach where the structural conservation of the charged residue pairs is analyzed among the pairs of homologous binary complexes. Specifically, we determine a large set of homologous interactions using an interaction interface similarity measure and catalog the basic types of conservation patterns among the charged residue pairs. We find an unexpected conservation pattern, which we call the correlated reappearance, occurring among the pairs of homologous interfaces more frequently than the fully conserved pairs of charged residues. Furthermore, the analysis of the conservation patterns across different superkingdoms as well as structural classes of proteins has revealed that the correlated reappearance of charged residues is by far the most prevalent conservation pattern, often occurring more frequently than the unconserved charged residues. We discuss a possible role that the new conservation pattern may play in the long-range electrostatic steering effect. 相似文献
1000.
Polyoxometalate/laccase-mediated oxidative polymerization of catechol for textile dyeing 总被引:1,自引:0,他引:1
Kim S Silva C Evtuguin DV Gamelas JA Cavaco-Paulo A 《Applied microbiology and biotechnology》2011,89(4):981-987
The synergistic effect between polyoxometalates (POMs), namely K5[SiW11VVO40]·11H2O and H5[PMo10VV
2O40]·13H2O and laccase from ascomycete Myceliophthora thermophila has been employed for the first time in oxidative polymerization of catechol. Such a laccase-mediator system allowed the
formation of a relatively high molecular weight polycatechol as confirmed by size exclusion chromatography and electrospray
ionization mass spectrometry (ESI-MS) (3990 Da when using K5[SiW11VVO40]·11H2O and 3600 Da with H5[PMo10VV
2O40]·13H2O). The synthesized polymers were applied as dyes for the dyeing of flax fabrics. The color intensity of flax fabrics colored
with polymer solutions was evaluated by diffuse reflectance spectrophotometry via k/s measurements (+10% of fixation ratio). A new synthetic process allowed a dyeing polymer, provided upon flax coloration, better
color fixation and color resistance when compared to that obtained by conventional synthesis with laccase solely or with addition
of organic mediator (1-hydroxybenzotriazole). 相似文献