全文获取类型
收费全文 | 2653篇 |
免费 | 341篇 |
国内免费 | 2篇 |
专业分类
2996篇 |
出版年
2021年 | 23篇 |
2018年 | 28篇 |
2017年 | 21篇 |
2016年 | 48篇 |
2015年 | 53篇 |
2014年 | 61篇 |
2013年 | 101篇 |
2012年 | 87篇 |
2011年 | 88篇 |
2010年 | 70篇 |
2009年 | 71篇 |
2008年 | 87篇 |
2007年 | 85篇 |
2006年 | 85篇 |
2005年 | 94篇 |
2004年 | 84篇 |
2003年 | 82篇 |
2002年 | 96篇 |
2001年 | 90篇 |
2000年 | 98篇 |
1999年 | 70篇 |
1998年 | 50篇 |
1997年 | 36篇 |
1996年 | 39篇 |
1995年 | 38篇 |
1994年 | 49篇 |
1993年 | 38篇 |
1992年 | 70篇 |
1991年 | 57篇 |
1990年 | 90篇 |
1989年 | 81篇 |
1988年 | 54篇 |
1987年 | 62篇 |
1986年 | 50篇 |
1985年 | 46篇 |
1984年 | 41篇 |
1983年 | 34篇 |
1982年 | 27篇 |
1981年 | 27篇 |
1980年 | 23篇 |
1979年 | 40篇 |
1978年 | 24篇 |
1977年 | 30篇 |
1976年 | 24篇 |
1973年 | 32篇 |
1972年 | 34篇 |
1971年 | 37篇 |
1970年 | 26篇 |
1969年 | 30篇 |
1968年 | 24篇 |
排序方式: 共有2996条查询结果,搜索用时 15 毫秒
991.
992.
993.
994.
Improvement of in-rumen digestibility of alfalfa forage by genetic manipulation of lignin O-methyltransferases 总被引:4,自引:0,他引:4
Guo Dianging Chen Fang Wheeler John Winder John Selman Susan Peterson Michael Dixon Richard A. 《Transgenic research》2001,10(5):457-464
Lignin inhibits forage digestibility by ruminant animals, and lignin levels and the proportion of dimethylated syringyl (S) lignin monomers increase with progressive maturity in stems of forage crops. We generated transgenic alfalfa (Medicago sativa L.) with reduced lignin content and altered lignin composition. Down-regulation of caffeic acid 3-O-methyltransferase (COMT) reduces lignin content, accompanied by near total loss of S lignin, whereas down-regulation of caffeoyl coenzyme A 3-O-methyltransferase (CCoAOMT) reduces lignin content without reduction in S lignin. These changes are not accompanied by altered ratios of cell wall polysaccharides. Analysis of rumen digestibility of alfalfa forage in fistulated steers revealed improved digestibility of forage from COMT down-regulated plants, but a greater improvement in digestibility following down-regulation of CCoAOMT. The results indicate that both lignin content and composition affect digestibility of alfalfa forage, and reveal a new strategy for forage quality improvement by genetic manipulation of CCoAOMT expression. 相似文献
995.
Binding Specificity of the Porphyromonas gingivalis Heme and Hemoglobin Receptor HmuR, Gingipain K, and Gingipain R1 for Heme, Porphyrins, and Metalloporphyrins 总被引:4,自引:0,他引:4 下载免费PDF全文
Teresa Olczak Dabney White Dixon Caroline Attardo Genco 《Journal of bacteriology》2001,183(19):5599-5608
Previous genetic and biochemical studies have confirmed that hemoglobin and hemin utilization in Porphyromonas gingivalis is mediated by the outer membrane hemoglobin and heme receptor HmuR, as well as gingipain K (Kgp), a lysine-specific cysteine protease, and gingipain R1 (HRgpA), one of two arginine-specific cysteine proteases. In this study we report on the binding specificity of the recombinant P. gingivalis HmuR protein and native gingipains for hemoglobin, hemin, various porphyrins, and metalloporphyrins as assessed by spectrophotometric assays, by affinity chromatography, and by enzyme-linked immunosorbent assay. Protoporphyrin, mesoporphyrin, deuteroporphyrin, hematoporphyrin, and some of their iron, copper, and zinc derivatives were examined to evaluate the role of both the central metal ion and the peripheral substituents on binding to recombinant HmuR and soluble gingipains. Scatchard analysis of hemin binding to Escherichia coli cells expressing recombinant membrane-associated six-His-tagged HmuR yielded a linear plot with a binding affinity of 2.4 x 10(-5) M. Recombinant E. coli cells bound the iron, copper, and zinc derivatives of protoporphyrin IX (PPIX) with similar affinities, and approximately four times more tightly than PPIX itself, which suggests that the active site of HmuR contains a histidine that binds the metal ion in the porphyrin ring. Furthermore, we found that recombinant HmuR prefers the ethyl and vinyl side chains of the PPIX molecule to either the larger hydroxyethyl or smaller hydrogen side chains. Kgp and HRgpA were demonstrated to bind various porphyrins and metalloporphyrins with affinities similar to those for hemin, indicating that the binding of Kgp and HRgpA to these porphyrins does not require a metal within the porphyrin ring. We did not detect the binding of RgpB, the arginine-specific cysteine protease that lacks a C-terminal hemagglutinin domain, to hemoglobin, porphyrins, or metalloporphyrins. Kgp and HRgpA, but not RgpB, were demonstrated to bind directly to soluble recombinant six-His-tagged HmuR. Several possible mechanisms for the cooperation between outer membrane receptor HmuR and proteases Kgp and HRgpA in hemin and hemoglobin binding and utilization are discussed. 相似文献
996.
Rebecca M. Dixon Jack R. Mellor Jonathan G. Hanley 《The Journal of biological chemistry》2009,284(21):14230-14235
Oxygen and glucose deprivation (OGD) induces delayed cell death in
hippocampal CA1 neurons via Ca2+/Zn2+-permeable,
GluR2-lacking AMPA receptors (AMPARs). Following OGD, synaptic AMPAR currents
in hippocampal neurons show marked inward rectification and increased
sensitivity to channel blockers selective for GluR2-lacking AMPARs. This
occurs via two mechanisms: a delayed down-regulation of GluR2 mRNA expression
and a rapid internalization of GluR2-containing AMPARs during the OGD insult,
which are replaced by GluR2-lacking receptors. The mechanisms that underlie
this rapid change in subunit composition are unknown. Here, we demonstrate
that this trafficking event shares features in common with events that mediate
long term depression and long term potentiation and is initiated by the
activation of N-methyl-d-aspartic acid receptors. Using
biochemical and electrophysiological approaches, we show that peptides that
interfere with PICK1 PDZ domain interactions block the OGD-induced switch in
subunit composition, implicating PICK1 in restricting GluR2 from synapses
during OGD. Furthermore, we show that GluR2-lacking AMPARs that arise at
synapses during OGD as a result of PICK1 PDZ interactions are involved in
OGD-induced delayed cell death. This work demonstrates that PICK1 plays a
crucial role in the response to OGD that results in altered synaptic
transmission and neuronal death and has implications for our understanding of
the molecular mechanisms that underlie cell death during stroke.Oxygen and glucose deprivation
(OGD)3 associated with
transient global ischemia induces delayed cell death, particularly in
hippocampal CA1 pyramidal cells
(1–3),
a phenomenon that involves Ca2+/Zn2+-permeable,
GluR2-lacking AMPARs (4).
AMPARs are heteromeric complexes of subunits GluR1–4
(5), and most AMPARs in the
hippocampus contain GluR2, which renders them calcium-impermeable and results
in a marked inward rectification in their current-voltage relationship
(6–8).
Ischemia induces a delayed down-regulation of GluR2 mRNA and protein
expression (4,
9–11),
resulting in enhanced AMPAR-mediated Ca2+ and Zn2+
influx into CA1 neurons (10,
12). In these neurons,
AMPAR-mediated postsynaptic currents (EPSCs) show marked inward rectification
1–2 days following ischemia and increased sensitivity to 1-naphthyl
acetyl spermine (NASPM), a channel blocker selective for GluR2-lacking AMPARs
(13–16).
Blockade of these channels at 9–40 h following ischemia is
neuroprotective, indicating a crucial role for Ca2+-permeable
AMPARs in ischemic cell death
(16).In addition to delayed changes in AMPAR subunit composition as a result of
altered mRNA expression, it was recently reported that
Ca2+-permable, GluR2-lacking AMPARs are targeted to synaptic sites
via membrane trafficking at much earlier times during OGD
(17). This subunit
rearrangement involves endocytosis of AMPARs containing GluR2 complexed with
GluR1/3, followed by exocytosis of GluR2-lacking receptors containing GluR1/3
(17). However, the molecular
mechanisms behind this trafficking event are unknown, and furthermore, it is
not known whether these trafficking-mediated changes in AMPAR subunit
composition contribute to delayed cell death.AMPAR trafficking is a well studied phenomenon because of its crucial
involvement in long term depression (LTD) and long term potentiation (LTP),
activity-dependent forms of synaptic plasticity thought to underlie learning
and memory. AMPAR endocytosis, exocytosis, and more recently subunit-switching
events (brought about by trafficking that involves endo/exocytosis) are
central to the necessary changes in synaptic receptor complement
(7,
18–20).
It is possible that similar mechanisms regulate AMPAR trafficking during
OGD.PICK1 is a PDZ and BAR (Bin-amphiphysin-Rus) domain-containing protein that
binds, via the PDZ domain, to a number of membrane proteins including AMPAR
subunits GluR2/3. This interaction is required for AMPAR internalization from
the synaptic plasma membrane in response to Ca2+ influx via NMDAR
activation in hippocampal neurons
(21–23).
This process is the major mechanism that underlies the reduction in synaptic
strength in LTD. Furthermore, PICK1-mediated trafficking has recently emerged
as a mechanism that regulates the GluR2 content of synaptic receptors, which
in turn determines their Ca2+ permeability
(7,
20). This is likely to be of
profound importance in both plasticity and pathological mechanisms.
Importantly, PICK1 overexpression has been shown to induce a shift in synaptic
AMPAR subunit composition in hippocampal CA1 neurons, resulting in inwardly
rectifying AMPAR EPSCs via reduced surface GluR2 and no change in GluR1
(24). This suggests that PICK1
may mediate the rapid switch in subunit composition occurring during OGD
(17). Here, we demonstrate
that the OGD-induced switch in AMPAR subunit composition is dependent on PICK1
PDZ interactions, and importantly, that this early trafficking event that
occurs during OGD contributes to the signaling that results in delayed
neuronal death. 相似文献
997.
998.
999.
Effectsof jasmonic acid (JA) and sucrose on tuber formation were studied in a commontuberous terrestrial orchid Pterostylis sanguinea D.L.Jones& M. Clements (dark banded greenhood orchid) from southwestern Australia.Seeds were germinated symbiotically in vitro on an oatmealagar (OMA) in the presence of a mycorrhizal fungus isolated from the orchidhost. Ten week-old seedlings were transferred into culture vessels containingOMA supplemented with JA (at concentrations 0, 0.1, 1, 5 or 10M), sucrose (at concentrations 0, 5, 10 or 20 gl–1) or combinations of each. Tuber development in alltreatments occurred approximately twenty-six weeks after seed sowing. Theaddition of 5 or 10 g l–1 sucrose with JA to themedia resulted in higher frequencies of tuber formation in comparison to thecontrol. Significantly higher proportion of seedlings produced tuber when themedium was supplemented with 5 g l–1 sucrose incombination with 5 M JA, compared to the control.In vitro tuber formation of Pterostylissanguinea can be improved by combined addition of appropriate levelsof JA and sucrose to OMA, which will aid in rapid in vitrotuberisation of terrestrial orchids. 相似文献
1000.
Characterization of a glycoprotein in the cyst fluid of Cysticercus tenuicollis from the goat 总被引:2,自引:0,他引:2
Dixon S. N., Gibbons R., Parker Janice and Sellwood R. 1973. Characterization of a glycoprotein in the cyst fluid of Cysticercus tenuicollis from the goat. International Journal for Parasitology3:419–424. In the fluids of two tapeworm cysts from goats a prominent periodic acid- Schiff reagent staining protein was found on gel electrophoretograms. In one case serum proteins from the host were also observed. The glycoprotein has been isolated and found to contain about 7·7 per cent heterosaccharide consisting of glucose, galactose, mannose, fucose, neuraminic acid, glucosamine and an unidentified component. The amino acid portion is extremely rich in glutamic acid, aspartic acid, lysine and arginine. Its molecular weight is approximately 90,000. A small degree of heterogeneity was demonstrated by ultra-centrifugal analysis; this may be due to the presence of about 3 per cent of a glycosaminoglycan. In view of the high proportion of charged amino acids it is suggested that this glycoprotein, which appears to be derived from the parasite, functions as the osmotically active macromolecule in the cyst fluid maintaining the turgidity of the cyst. 相似文献