全文获取类型
收费全文 | 13607篇 |
免费 | 1069篇 |
国内免费 | 2篇 |
出版年
2023年 | 70篇 |
2022年 | 157篇 |
2021年 | 272篇 |
2020年 | 161篇 |
2019年 | 194篇 |
2018年 | 262篇 |
2017年 | 253篇 |
2016年 | 413篇 |
2015年 | 671篇 |
2014年 | 769篇 |
2013年 | 934篇 |
2012年 | 1268篇 |
2011年 | 1184篇 |
2010年 | 710篇 |
2009年 | 631篇 |
2008年 | 912篇 |
2007年 | 950篇 |
2006年 | 788篇 |
2005年 | 773篇 |
2004年 | 682篇 |
2003年 | 650篇 |
2002年 | 641篇 |
2001年 | 111篇 |
2000年 | 84篇 |
1999年 | 112篇 |
1998年 | 147篇 |
1997年 | 92篇 |
1996年 | 77篇 |
1995年 | 76篇 |
1994年 | 78篇 |
1993年 | 75篇 |
1992年 | 56篇 |
1991年 | 50篇 |
1990年 | 42篇 |
1989年 | 34篇 |
1988年 | 27篇 |
1987年 | 23篇 |
1986年 | 24篇 |
1985年 | 16篇 |
1984年 | 22篇 |
1983年 | 20篇 |
1982年 | 10篇 |
1981年 | 17篇 |
1980年 | 15篇 |
1979年 | 12篇 |
1978年 | 14篇 |
1975年 | 8篇 |
1971年 | 11篇 |
1969年 | 8篇 |
1966年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
121.
Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI. 总被引:7,自引:1,他引:6
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
L Shiue J Green O M Green J L Karas J P Morgenstern M K Ram M K Taylor M J Zoller L D Zydowsky J B Bolen et al. 《Molecular and cellular biology》1995,15(1):272-281
Activation of protein tyrosine kinases is one of the initial events following aggregation of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on RBL-2H3 cells, a model mast cell line. The protein tyrosine kinase p72syk (Syk), which contains two Src homology 2 (SH2) domains, is activated and associates with phosphorylated Fc epsilon RI subunits after receptor aggregation. In this report, we used Syk SH2 domains, expressed in tandem or individually, as fusion proteins to identify Syk-binding proteins in RBL-2H3 lysates. We show that the tandem Syk SH2 domains selectively associate with tyrosine-phosphorylated forms of the gamma and beta subunits of Fc epsilon RI. The isolated carboxy-proximal SH2 domain exhibited a significantly higher affinity for the Fc epsilon RI subunits than did the amino-proximal domain. When in tandem, the Syk SH2 domains showed enhanced binding to phosphorylated gamma and beta subunits. The conserved tyrosine-based activation motifs contained in the cytoplasmic domains of the gamma and beta subunits, characterized by two YXXL/I sequences in tandem, represent potential high-affinity binding sites for the dual SH2 domains of Syk. Peptide competition studies indicated that Syk exhibits a higher affinity for the phosphorylated tyrosine activation motif of the gamma subunit than for that of the beta subunit. In addition, we show that Syk is the major protein in RBL-2H3 cells that is affinity isolated with phosphorylated peptides corresponding to the phosphorylated gamma subunit motif. These data suggest that Syk associates with the gamma subunit of the high-affinity receptor for immunoglobulin E through an interaction between the tandem SH2 domains of SH2 domains of Syk and the phosphorylated tyrosine activation motif of the gamma subunit and that Syk may be the major signaling protein that binds to Fc epsilon RI tyrosine activation motif of the gamma subunit and that Syk may be the major signaling protein that binds to Dc epsilon tyrosine activation motifs in RBL-2H3 cells. 相似文献
122.
Johannes Becker-Follmann Andreas Gaa Elke Baùsch Ernst Natt Gerd Scherer Otto von Deimling 《Mammalian genome》1997,8(3):172-177
We have performed a high-resolution linkage analysis for the conserved segment on distal mouse Chromosome (Chr) 8 that is
homologous to human Chr 16q. The interspecific backcross used involved M. m. molossinus and an M. m. domesticus line congenic for an M. spretus segment from Chr 8 flanked by phenotypic markers Os (oligosyndactyly) and e, a coat colormarker. From a total of 682 N2 progeny, the 191 animals revealing a recombination event between these phenotypic markers were typed for 23 internal loci.
The following locus order with distances in cM was obtained: (centromere)–Os–4.1–Mmp2–0.2–Ces1,Es1, Es22–1.2–Mt1,D8Mit15–2.2–Got2, D8Mit11–3.7–Es30–0.3–Es2, Es7–0.9–Ctra1,Lcat–0.3–Cdh1, Cadp, Nmor1, D8Mit12–0.2–Mov34–2.5–Hp,Tat–0.2–Zfp4–1.6–Zfp1,Ctrb–10.9–e. In a separate interspecific cross involving 62 meioses, Dpep1 was mapped together with Aprt and Cdh3 at 12.9 cM distal to Hp, Tat, to the vicinity of e. Our data give locus order for markers not previously resolved, add Mmp2 and Dpep1 as new markers on mouse Chr 8, and indicate that Ctra1 is the mouse homolog for human CTRL. Comparison of the order of 17 mouse loci with that of their human homologs reveals that
locus order is well conserved and that the conserved segment in the human apparently spans the whole long arm of Chr 16.
Received: 30 July 1996 / Accepted: 15 November 1996 相似文献
123.
124.
125.
Expression of TRPC3 in Chinese Hamster Ovary Cells Results in Calcium-activated Cation Currents Not Related to Store Depletion 总被引:16,自引:0,他引:16
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Christof Zitt Alexander G. Obukhov Carsten Strübing Andrea Zobel Frank Kalkbrenner Andreas Lückhoff Günter Schultz 《The Journal of cell biology》1997,138(6):1333-1341
TRPC3 (or Htrp3) is a human member of the trp family of Ca2+-permeable cation channels. Since expression of TRPC3 cDNA results in markedly enhanced Ca2+ influx in response to stimulation of membrane receptors linked to phospholipase C (Zhu, X., J. Meisheng, M. Peyton, G. Bouley, R. Hurst, E. Stefani, and L. Birnbaumer. 1996. Cell. 85:661–671), we tested whether TRPC3 might represent a Ca2+ entry pathway activated as a consequence of depletion of intracellular calcium stores. CHO cells expressing TRPC3 after intranuclear injection of cDNA coding for TRPC3 were identified by fluorescence from green fluorescent protein. Expression of TRPC3 produced cation currents with little selectivity for Ca2+ over Na+. These currents were constitutively active, not enhanced by depletion of calcium stores with inositol-1,4,5-trisphosphate or thapsigargin, and attenuated by strong intracellular Ca2+ buffering. Ionomycin led to profound increases of currents, but this effect was strictly dependent on the presence of extracellular Ca2+. Likewise, infusion of Ca2+ into cell through the patch pipette increased TRPC3 currents. Therefore, TRPC3 is stimulated by a Ca2+-dependent mechanism. Studies on TRPC3 in inside-out patches showed cation-selective channels with 60-pS conductance and short (<2 ms) mean open times. Application of ionomycin to cells increased channel activity in cell-attached patches. Increasing the Ca2+ concentration on the cytosolic side of inside-out patches (from 0 to 1 and 30 μM), however, failed to stimulate channel activity, even in the presence of calmodulin (0.2 μM). We conclude that TRPC3 codes for a Ca2+-permeable channel that supports Ca2+-induced Ca2+-entry but should not be considered store operated. 相似文献
126.
127.
NMDA Receptor Heterogeneity During Postnatal Development of the Rat Brain: Differential Expression of the NR2A, NR2B, and NR2C Subunit Proteins 总被引:17,自引:3,他引:14
Andreas Wenzel Jean Marc Fritschy Hanns Mohler Dietmar Benke 《Journal of neurochemistry》1997,68(2):469-478
Abstract: Changes in the expression of the NMDA receptor subunits (NRs) NR2A, 2B, and 2C were investigated in histo blots of the developing rat brain with subunit-specific antisera. At birth, the NR2B subunit was detected almost ubiquitously, the NR2A subunit staining was faint and restricted to the hippocampus, cerebral cortex, and striatum, and no NR2C subunit immunoreactivity was detected. During the first 3 postnatal weeks, the NR2B subunit became confined to forebrain structures, whereas the NR2A immunoreactivity became abundantly expressed throughout the brain. The NR2C immunoreactivity emerged 5 days after birth in the olfactory bulb, thalamus, and vestibular nuclei and became very intense after 10 days in cerebellar granule cells, its primary site of expression in adulthood. After 3 weeks, NR2A and NR2B immunoreactivity decreased to adult levels, whereas NR2C immunoreactivity remained unchanged. The patterns of distribution of the subunit proteins were in agreement with those of their corresponding mRNAs, as monitored by in situ hybridization histochemistry, although the mRNA translation appeared to be delayed by several days in certain areas. Our results reveal a progressive increase in the heterogeneity of NMDA receptors due to the comparably late onset of NR2A and NR2C subunit expression and by the area-specific rearrangement of NR2B subunit expression following birth. 相似文献
128.
Theodorou Andreas; Weger Natalie; Kunke Kathleen; Rhee Kyoo; Bice David; Muggenberg Bruce; Lemen Richard 《Journal of applied physiology》1997,83(3):912-917
Theodorou, Andreas, Natalie Weger, Kathleen Kunke, KyooRhee, David Bice, Bruce Muggenberg, and Richard Lemen. Ragweed sensitization alters pulmonary vascular responses to bronchoprovocation in beagle dogs. J. Appl. Physiol.83(3): 912-917, 1997.In ragweed (RW)-sensitized beagle dogs, wetested the hypothesis that reactivity of the pulmonary vasculature wasenhanced with aerosolized histamine (Hist) and RW. Seven dogs wereneonatally sensitized with repeated intraperitoneal RW injections, and12 dogs were controls (Con). The dogs were anesthetizedwith intravenous chloralose, mechanically ventilated, and instrumentedwith femoral arterial and pulmonary artery catheters. Specific lungcompliance(CLsp),specific lung conductance (Gsp),systemic vascular resistance index, and pulmonary vascular resistanceindex (PVRI) were measured before and after bronchoprovocation withHist and RW. After Hist inhalation (5 breaths of 30 mg/ml), both Conand RW dogs had significant (P < 0.05) decreases inCLsp(51 ± 4 and 53 ± 5%, respectively) andGsp (65 ± 5 and69 ± 3%, respectively), but only RW-sensitized dogs had asignificant increase in PVRI (38 ± 10%). After RW inhalation (60 breaths of 0.8 mg/ml), only RW-sensitized dogs had significant increases (62 ± 20%) in PVRI and decreases inGsp (77 ± 4%) and CLsp(65 ± 7%). We conclude that, compared with Con,RW-sensitized beagle dogs have increased pulmonary vasoconstrictiveresponses with Hist or RW inhalation. 相似文献
129.
A close association between the HIV surface protein gp120 and the CD4 T cell receptor initiates the viral multiplication cycle. A 15 amino acid peptide (LAV) within the CD4 binding domain of gp 120 has been shown to retain receptor binding ability. The structural behavior of the LAV peptide has been studied by CD and NMR methods in aqueous solution and upon addition of trifluoroethanol (TFE) to emulate the relatively apolar conditions at the membrane bound receptor. Previous work has shown that the LAV peptide folds into a β-pleated structure in more polar buffer/TFE mixtures, while a concerted structural change can be observed at a concentration of 60% TFE (v/v). This abrupt, cooperative refolding from a regular β-sheet to a helical secondary structure is known as “switch” behavior. Former CD experiments with LAV sequence variants have supported the assumption that four amino acids at the N-terminus (LPCR) are indispensable for the “switch.” The tetrad has a strong β-turn forming potential. The suggestion has been formulated that the tetrad can act as a nucleation site governing the refolding. The present NMR study of the LAV peptide in TFE gives evidence for a 310-helix suggesting that the tetrad adopts a type III β-turn and promotes the formation of a similar bend in the next overlapping tetrad until the sequence is restructured into a 310-helix at a critical polarity favoring intrachain hydrogen bonds. © 1995 Wiley-Liss, Inc. 相似文献
130.
Klaus Kayser Sabine André Gerhard Böhm Sonia Donaldo-Jacinto Peter Fritz Herbert Kaltner Gian Kayser Wolf-Peter Kunze Andreas Nehrlich Fu-Yue Zeng Hans-Joachim Gabius 《Development genes and evolution》1995,204(5):344-349
Protein-carbohydrate interactions are supposed to play key roles in the mechanisms of cell adhesion, biosignalling and intracellular routing, warranting the analysis of the developmental course of expression of epitopes of this system. Thus, a panel of carrier-immobilized carbohydrate ligands was used as probes, namely lactose,N-acetylgalactosamine,N-acetylglucosamine, mannose, fucose and maltose. Additionally, an antibody to an endogenous -galactoside-binding lectin (anti-galectin-1), the biotinylated lectin and two further human lectins, namely the macrophage migration inhibitory factor-binding sarcolectin and serum amyloid P component (SAP) that displays selectivity for sulphated sugars and mannose-6-phosphate, were included. They enabled us to assess the extent of the presence of respective binding sites in fixed sections from human lungs (pulmonary epithelial cells), livers (hepatocytes) and hearts (myocard cells) of 10–50 weeks gestation. Invariably, specific binding was detected in the three organ types, at least in certain stages. In most of the cases, the intensity of staining exhibited developmental regulation. The apparent patterns reveal similarities between the different cell types, as seen with immobilizedN-acetylglucosamine as well as with labelled galectin-1 and sarcolectin. However, drastic differences among such patterns with nearly opposite developmental courses do also occur, as detected for carrier-attached mannose and maltose residues. These results point to a potential importance for the detected glycohistochemical features in human development and substantiate the possibility of differential regulation of the presence of binding sites for distinct sugars within a certain organ and between the individual cell types of the monitored organs. 相似文献