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71.
Olivia Molinar-Inglis Jacob M. Wozniak Neil J. Grimsey Lennis B. Ordua-Castillo Norton Cheng Ying Lin Monica L. Gonzalez Ramirez Cierra A. Birch John D. Lapek David J. Gonzalez JoAnn Trejo 《The Journal of biological chemistry》2022,298(4)
Endothelial dysfunction is a hallmark of inflammation and is mediated by inflammatory factors that signal through G protein–coupled receptors including protease-activated receptor-1 (PAR1). PAR1, a receptor for thrombin, signals via the small GTPase RhoA and myosin light chain intermediates to facilitate endothelial barrier permeability. PAR1 also induces endothelial barrier disruption through a p38 mitogen-activated protein kinase–dependent pathway, which does not integrate into the RhoA/MLC pathway; however, the PAR1-p38 signaling pathways that promote endothelial dysfunction remain poorly defined. To identify effectors of this pathway, we performed a global phosphoproteome analysis of thrombin signaling regulated by p38 in human cultured endothelial cells using multiplexed quantitative mass spectrometry. We identified 5491 unique phosphopeptides and 2317 phosphoproteins, four distinct dynamic phosphoproteome profiles of thrombin-p38 signaling, and an enrichment of biological functions associated with endothelial dysfunction, including modulators of endothelial barrier disruption and a subset of kinases predicted to regulate p38-dependent thrombin signaling. Using available antibodies to detect identified phosphosites of key p38-regulated proteins, we discovered that inhibition of p38 activity and siRNA-targeted depletion of the p38α isoform increased basal phosphorylation of extracellular signal–regulated protein kinase 1/2, resulting in amplified thrombin-stimulated extracellular signal–regulated protein kinase 1/2 phosphorylation that was dependent on PAR1. We also discovered a role for p38 in the phosphorylation of α-catenin, a component of adherens junctions, suggesting that this phosphorylation may function as an important regulatory process. Taken together, these studies define a rich array of thrombin- and p38-regulated candidate proteins that may serve important roles in endothelial dysfunction. 相似文献
72.
Biologic drugs, such as monoclonal antibodies, are commonly made using mammalian cells in culture. The cell lines used for manufacturing should ideally be clonal, meaning derived from a single cell, which represents a technically challenging process. Fetal bovine serum is often used to support low cell density cultures, however, from a regulatory perspective, it is preferable to avoid animal‐derived components to increase process consistency and reduce the risk of contamination from adventitious agents. Chinese hamster ovary (CHO) cells are the most widely used cell line in industry and a large number of serum‐free, protein‐free, and fully chemically defined growth media are commercially available, although these media alone do not readily support efficient single cell cloning. In this work, we have developed a simple, fully defined, single‐cell cloning media, specifically for CHO cells, using commercially available reagents. Our results show that a 1:1 mixture of CD‐CHO? and DMEM/F12 supplemented with 1.5 g/L of recombinant albumin (Albucult®) supports single cell cloning. This formulation can support recovery of single cells in 43% of cultures compared to 62% in the presence of serum. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012 相似文献
73.
74.
Laponogov I Veselkov DA Sohi MK Pan XS Achari A Yang C Ferrara JD Fisher LM Sanderson MR 《PloS one》2007,2(3):e301
The 2.7 A crystal structure of the 55-kDa N-terminal breakage-reunion domain of topoisomerase (topo) IV subunit A (ParC) from Streptococcus pneumoniae, the first for the quinolone targets from a gram-positive bacterium, has been solved and reveals a 'closed' dimer similar in fold to Escherichia coli DNA gyrase subunit A (GyrA), but distinct from the 'open' gate structure of Escherichia coli ParC. Unlike GyrA whose DNA binding groove is largely positively charged, the DNA binding site of ParC exhibits a distinct pattern of alternating positively and negatively charged regions coincident with the predicted positions of the grooves and phosphate backbone of DNA. Based on the ParC structure, a new induced-fit model for sequence-specific recognition of the gate (G) segment by ParC has been proposed. These features may account for the unique DNA recognition and quinolone targeting properties of pneumococcal type II topoisomerases compared to their gram-negative counterparts. 相似文献
75.
Cheng Ly Tamar Melman Alison L. Barth G. Bard Ermentrout 《Journal of computational neuroscience》2011,30(2):211-223
BK channels are large conductance potassium channels gated by calcium and voltage. Paradoxically, blocking these channels has been shown experimentally to increase or decrease the firing rate of neurons, depending on the neural subtype and brain region. The mechanism for how this current can alter the firing rates of different neurons remains poorly understood. Using phase-resetting curve (PRC) theory, we determine when BK channels increase or decrease the firing rates in neural models. The addition of BK currents always decreases the firing rate when the PRC has only a positive region. When the PRC has a negative region (type II), BK currents can increase the firing rate. The influence of BK channels on firing rate in the presence of other conductances, such as I m and I h , as well as with different amplitudes of depolarizing input, were also investigated. These results provide a formal explanation for the apparently contradictory effects of BK channel antagonists on firing rates. 相似文献
76.
Eugen F. Mesaros Jason P. BurkeJonathan D. Parrish Benjamin J. DuganAndrew V. Anzalone Thelma S. AngelesMark S. Albom Lisa D. AimoneMatthew R. Quail Weihua WanLihui Lu Zeqi HuangMark A. Ator Bruce A. RuggeriMangeng Cheng Gregory R. Ott Bruce D. Dorsey 《Bioorganic & medicinal chemistry letters》2011,21(6):1900
77.
78.
ARF-GTPase activating protein mediates auxin influx carrier AUX1 early endosome trafficking to regulate auxin dependent plant development 总被引:1,自引:0,他引:1
Polar auxin transport (PAT) plays a critical role in the regulation of plant growth and development. Auxin influx carrier AUX1 is predominantly localized to the upper side of specific root cells in Arabidopsis. Overexpression of OsAGAP, an ARF-GTPase activating protein in rice, could induce the accumulation of AUX1. But the mechanism is poorly known. Here we reported that over-expression of ARF-GAP could reduce the thickness and bundling of microfilament (MF) which possibly could greatly interfere with the endocytosis of AUX1 early endosome; but not the exocytosis of AUX1 recycling endosome. Therefore, AFR-GAP over-expression suppressed-MF bundling is likely involved in regulating endocytosis of Auxin influx carrier AUX1 and in mediating auxin dependent plant development. 相似文献
79.
本文报道了中国苋科苋属的一新记录归化植物——广布苋(Amaranthus graecizans L.)。该种植株常匍匐,叶片狭长椭圆形至线状披针形,有时线形或菱形卵形,长至少为宽的2.5倍,花被片3枚,近等长,与中国有分布的本属其他物种有所区别。该种原产于欧洲地中海地区、非洲北部至亚洲西部,归化于欧洲其他地区、东亚、澳大利亚、北美洲以及我国的河南、河北和山东等地区。该种易与苋属其他种类相混淆,因此其在我国的分布区可能被低估。此外,本文还对该种的种下等级以及该种的相似种进行了区分,并对该种下亚种Amaranthus graecizans subsp. thellungianus (Nevski) Gusev与国内文献记载的腋花苋(Amaranthus roxburghianus Kung)之间的关系作了说明与澄清。 相似文献
80.
Organic Solar Cells: Following the Morphology Formation In Situ in Printed Active Layers for Organic Solar Cells (Adv. Energy Mater. 1/2016) 下载免费PDF全文