全文获取类型
收费全文 | 359篇 |
免费 | 29篇 |
国内免费 | 9篇 |
专业分类
397篇 |
出版年
2022年 | 4篇 |
2021年 | 1篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 17篇 |
2014年 | 15篇 |
2013年 | 23篇 |
2012年 | 14篇 |
2011年 | 24篇 |
2010年 | 16篇 |
2009年 | 9篇 |
2008年 | 15篇 |
2007年 | 15篇 |
2006年 | 14篇 |
2005年 | 13篇 |
2004年 | 20篇 |
2003年 | 12篇 |
2002年 | 10篇 |
2001年 | 19篇 |
2000年 | 11篇 |
1999年 | 10篇 |
1998年 | 11篇 |
1997年 | 12篇 |
1996年 | 11篇 |
1995年 | 2篇 |
1994年 | 9篇 |
1993年 | 8篇 |
1992年 | 2篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 8篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1977年 | 5篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1959年 | 2篇 |
1955年 | 1篇 |
1954年 | 2篇 |
1931年 | 1篇 |
1927年 | 1篇 |
1918年 | 1篇 |
排序方式: 共有397条查询结果,搜索用时 15 毫秒
91.
铁皮石斛的离体开花 总被引:9,自引:0,他引:9
铁皮石斛(Dendrobium candidum),为一种野生兰科植物,在栽培条件下,从种子萌发到开花通常需要3~4a.研究了多种植物激素和多胺对该种石斛组织培养中花芽形成的影响,结果表明在培养基中加入合适浓度的亚精胺(spermidine)或BA(6-苄基腺嘌呤),或同时加入NAA(萘乙酸)和BA均可诱导原球茎或由之形成的无根小苗在3~6个月开花,频率在31.6%~45.8%.当将原球茎在加有ABA(脱落酸)的培养基上预培养后再移到加有BA的培养基上,花芽形成的频率可提高到平均达82.8%(个别实验中可达100%),这种诱导提早开花的现象也与实验材料的发育阶段(原球茎、无根小苗、已生根的小苗)有关,通常发生在根的形成受到完全或部分抑制的情况中. 相似文献
92.
Tyrosine phosphorylation of Munc18‐1 inhibits synaptic transmission by preventing SNARE assembly 下载免费PDF全文
Marieke Meijer Bernhard Dörr Hanna CA Lammertse Chrysanthi Blithikioti Jan RT van Weering Ruud FG Toonen Thomas H Söllner Matthijs Verhage 《The EMBO journal》2018,37(2):300-320
Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18‐1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho‐proteomics abolished the stimulatory effect of Munc18‐1 on SNARE complex formation (“SNARE‐templating”) and membrane fusion in vitro. Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18‐1‐null neurons expressing Munc18‐1Y473D. Synaptic transmission was temporarily restored by high‐frequency stimulation, as well as by a Munc18‐1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming. On the other hand, expression of non‐phosphorylatable Munc18‐1 supported normal synaptic transmission. We propose that SFK‐dependent Munc18‐1 phosphorylation may constitute a potent, previously unknown mechanism to shut down synaptic transmission, via direct occlusion of a Synaptobrevin/VAMP2 binding groove and subsequent hindrance of conformational changes in domain 3a responsible for vesicle priming. This would strongly interfere with the essential post‐docking SNARE‐templating role of Munc18‐1, resulting in a largely abolished pool of releasable synaptic vesicles. 相似文献
93.
目的:探讨胸内正压对正常人左室射血及充盈的影响及其力学原理。方法:超声心动图观测30例正常人初始时与标准乏氏动作张力期10s时左室舒张末容积(LVEDV)、左室收缩末容积(LVESV)、每搏量(SV)、射血分值(EF)、流入道血流速度(E峰、A峰)、E/A值、二尖瓣环舒张早期运动速度(e)及舒张早期充盈压(E/e)的变化。结果:与初始时比较,标准乏氏动作张力期LVEDV、LVESV及SV减低而心率(陬)增快(P均〈0.001),EF值增加,但无统计学意义(P〉0.05);E峰与E/A值减低(P均〈O.05);e没有变化(P〉0.05).E/e值减低(P〈O.05)。结论:胸内正压对左室游离壁的力学作用促进了左室收缩运动而阻碍了左室舒张运动,会引起EF值增加,E峰及E/A值减低;2,胸内正压降低了肺静脉系统与心脏的跨壁压力,增加了血流阻力也是导致肺静脉系统与左室血液回流减少.E峰减低.E/e值减低的一个原因。 相似文献
94.
Fucose is a major constituent of the protein- and lipid-linked glycans of
the various life-cycle stages of schistosomes. These fucosylated glycans
are highly antigenic and seem to play a role in the pathology of
schistosomiasis. In this article we describe the identification and
characterization of two fucosyltransferases (FucTs) in cercariae of the
avian schistosome Trichobilharzia ocellata, a GDP-Fuc:[Galbeta1--
>4]GlcNAcbeta-R alpha1-->3-FucT and a novel GDP-Fuc:Fucalpha-R
alpha1-- >2-FucT. Triton X-100 extracts of cercariae were assayed for
FucT activity using a variety of acceptor substrates. Type 1 chain
(Galbeta1- ->3GlcNAc) based compounds were poor acceptors, whereas those
based on a type 2 chain (Galbeta1-->4GlcNAc), whether
alpha2'-fucosylated, alpha3'-sialylated, or unsubstituted, and whether
present as oligosaccharide or contained in a glycopeptide or glycoprotein,
all served as acceptor substrates. In this respect the schistosomal alpha3-
FucT resembles human FucT V and VI rather than other known FucTs. N-
ethylmaleimide, an inhibitor of several human FucTs, had no effect on the
activity of the schistosomal alpha3-FucT, whereas GDP-beta-S was strongly
inhibitory. Large scale incubations were carried out with
Galbeta1-->4GlcNAc, GalNAcbeta1-->4GlcNAcbeta-O -(CH2)8COOCH3 and
Fucalpha1-->3GlcNAcbeta1-->2Man as acceptor substrates and the
products of the incubations were isolated using a sequence of
chromatographic techniques. By methylation analysis and 2D-TOCSY and
ROESY1H-NMR spectroscopy the products formed were shown to be Galbeta1--
>4[Fucalpha1-->2Fucalpha1-->3]GlcNAc,
GalNAcbeta1-->4[Fucalpha1-- >2Fucalpha1-->3]GlcNAcbe
ta-O-(CH2)8COOCH3, and Fucalpha1-->2Fucalpha1--
>3GlcNAcbeta1-->2Man, respectively. It is concluded that the alpha2-
FucT and alpha3-FucT are involved in the biosynthesis of the (oligomeric)
Lewisx sequences and the Fucalpha1-->2Fucalpha1-->3GlcNAc structural
element that have been described on schistosomal glycoconjugates.
相似文献
95.
Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage. 总被引:9,自引:0,他引:9 下载免费PDF全文
K Chapman Z Mustafa C Irven A J Carr K Clipsham A Smith J Chitnavis J S Sinsheimer V A Bloomfield M McCartney O Cox L R Cardon B Sykes J Loughlin 《American journal of human genetics》1999,65(1):167-174
We present a two-stage genomewide scan for osteoarthritis-susceptibility loci, using 481 families that each contain at least one affected sibling pair. The first stage, with 272 microsatellite markers and 297 families, involved a sparse map covering 23 chromosomes at intervals of approximately 15 cM. Sixteen markers that showed evidence of linkage at nominal P=.05 were then taken through to the second stage, with an additional 184 families. This second stage confirmed evidence of linkage for markers on chromosome 11q. Additional markers from this region were then typed to create a denser map. We obtained a maximum single-point LOD score, at D11S901, of 2.40 (P=.0004) and a maximum multipoint-LOD score of 3.15, between markers D11S1358 and D11S35. A subset of 196 of the 481 families, comprising affected female sibling pairs, generated a corrected LOD score of 2.54 (P=.0003) for marker D11S901, with evidence for linkage extending 12 cM proximal to this marker. When we stratified for affected male sibling pairs there was no evidence of linkage to chromosome 11. Our data suggest that a female-specific susceptibility gene for idiopathic osteoarthritis is located on chromosome 11q. 相似文献
96.
Microbial Species Involved in Production of 1,2-sn-Diacylglycerol and Effects of Phosphatidylcholine on Human Fecal Microbiota 下载免费PDF全文
Jelena Vulevic Anne L. McCartney Jennifer M. Gee Ian T. Johnson Glenn R. Gibson 《Applied microbiology》2004,70(9):5659-5666
1,2-sn-Diacylglycerols (DAGs) are activators of protein kinase C (PKC), which is involved in the regulation of colonic mucosal proliferation. Extracellular DAG has been shown to stimulate the growth of cancer cell lines in vitro and may therefore play an important role in tumor promotion. DAG has been detected in human fecal extracts and is thought to be of microbial origin. Hitherto, no attempts have been made to identify the predominant fecal bacterial species involved in its production. We therefore used anaerobic batch culture systems to determine whether fecal bacteria could utilize phosphatidylcholine (0.5% [wt/vol]) to produce DAG. Production was found to be dependent upon the presence of the substrate and was enhanced in the presence of high concentrations of deoxycholate (5 and 10 mM) in the growth medium. Moreover, its production increased with the pH, and large inter- and intraindividual variations were observed between cultures seeded with inocula from different individuals. Clostridia and Escherichia coli multiplied in the fermentation systems, indicating their involvement in phosphatidylcholine metabolism. On the other hand, there was a significant decrease in the number of Bifidobacterium spp. in the presence of phosphatidylcholine. Pure-culture experiments showed that 10 of the 12 strains yielding the highest DAG levels (>50 nmol/ml) were isolated from batch culture enrichments run at pH 8.5. We found that the strains capable of producing large amounts of DAG were predominantly Clostridium bifermentans (8 of 12), followed by Escherichia coli (2 of 12). Interestingly, one DAG-producing strain was Bifidobacterium infantis, which is often considered a beneficial gut microorganism. Our results have provided further evidence that fecal bacteria can produce DAG and that specific bacterial groups are involved in this process. Future strategies to reduce DAG formation in the gut should target these species. 相似文献
97.
McCartney CR Bellows AB Gingrich MB Hu Y Evans WS Marshall JC Veldhuis JD 《American journal of physiology. Endocrinology and metabolism》2004,286(6):E902-E908
Studies using pharmacological gonadotropin stimulation suggest that ovarian steroidogenesis is abnormal in the polycystic ovary syndrome (PCOS). We assessed ovarian steroid secretion in response to near-physiological gonadotropin stimuli in 12 ovulatory controls and 7 women with PCOS. A gonadotropin-releasing hormone-receptor antagonist (ganirelix, 2 mg sc) was given to block endogenous LH secretion, followed by dexamethasone (0.75 mg orally) to suppress adrenal androgen secretion. After ganirelix injection (12 h), intravenous infusions of recombinant human LH (0, 10, 30, 100, and 300 IU; each over 8 min) were administered at 4-h intervals in a pseudorandomized (highest dose last) manner. Plasma LH, 17-hydroxyprogesterone (17-OHP), androstenedione, and testosterone were measured concurrently. LH dose-steroid response relationships (mean sex-steroid concentration vs. mean LH concentration over 4 h postinfusion) were examined for each subject. Linear regression of 17-OHP on LH yielded a higher (mean +/- SE) slope in PCOS (0.028 +/- 0.010 vs. 0.005 +/- 0.005, P < 0.05), whereas extrapolated 17-OHP at zero LH was similar. The slopes of other regressions did not differ from zero in either PCOS or controls. We conclude that near-physiological LH stimulation drives heightened 17-OHP secretion in patients with PCOS, suggesting abnormalities of early steps of ovarian steroidogenesis. With the exception of 17-OHP response in PCOS, no acute LH dose-ovarian steroid responses were observed in controls or PCOS. Defining the precise mechanistic basis of heightened precursor responsiveness to LH in PCOS will require further clinical investigation. 相似文献
98.
The yeast Snf1 kinase and its metazoan orthologues, the AMP-activated protein kinases, are activated in response to nutrient limitation. Activation requires the phosphorylation of a conserved threonine residue in the activation loop of the catalytic subunit. A phosphopeptide antibody was generated that specifically recognizes Snf1 protein that is phosphorylated in its activation loop on threonine 210. Using this reagent, we show that phosphorylation of threonine 210 correlates with Snf1 activity, since it is detected in cells subjected to glucose limitation but not in cells grown in abundant glucose. A Snf1 mutant completely lacking kinase activity was phosphorylated normally on threonine 210 in glucose-starved cells, eliminating the possibility that the threonine 210 modification is due to an autophosphorylation event. Cells lacking the Reg1 protein, a regulatory subunit for the Glc7 phosphatase, showed constitutive phosphorylation of Snf1 threonine 210. Exposure of cells to high concentrations of sodium chloride also induced phosphorylation of Snf1. Interestingly, Mig1, a downstream target of Snf1 kinase, is phosphorylated in glucose-stressed but not sodium-stressed cells. Finally, cells lacking the gamma subunit of the Snf1 kinase complex encoded by the SNF4 gene exhibited normal regulation of threonine 210 phosphorylation in response to glucose limitation but are unable to phosphorylate Mig1 efficiently. Our data indicate that activation of the Snf1 kinase complex involves two steps, one that requires a distinct upstream kinase and one that is mediated by the gamma subunit of the kinase itself. 相似文献
99.
Stuart M Phillips Brian G Stewart Douglas J Mahoney Audrey L Hicks Neil McCartney Jason E Tang Sarah B Wilkinson David Armstrong Mark A Tarnopolsky 《Journal of applied physiology》2004,97(2):716-724
The impact of a 6-mo body-weight-supported treadmill training program on glucose homeostasis and muscle metabolic characteristics was investigated. Nine individuals (31 +/- 3 yr, 8.1 +/- 2.5 yr postinjury; means +/- SE) with incomplete spinal cord injury trained three times weekly for a total of 6 mo. Training session duration and intensity (velocity) increased by 54 +/- 10% (P < 0.01) and 135 +/- 20%, respectively. Muscle biopsies and a modified glucose tolerance test (100 g glucose with [U-(13)C]glucose) were performed before (Pre) and after training (Post). Training resulted in a reduction in area under the curve of glucose x time (-15 +/- 4%) and insulin x time (-33 +/- 8%; both P < 0.05). Oxidation of exogenous (ingested) glucose increased as a result of training (Pre = 4.4 +/- 0.7 g/h, Post = 7.4 +/- 0.6 g/h; P < 0.05), as did oxidation of endogenous (liver) glucose (Pre = 3.8 +/- 0.3 g/h, Post = 5.2 +/- 0.3 g/h; P < 0.05). Training resulted in increased muscle glycogen (80 +/- 23%; P < 0.05) and GLUT-4 content and hexokinase II enzyme activity (126 +/- 34 and 49 +/- 4%, respectively, both P < 0.01). Resting muscle phosphocreatine content also increased after training (Pre = 62.1 +/- 4.3, Post = 78.7 +/- 3.8, both mmol/kg dry wt and P < 0.05). Six months of thrice-weekly body-weight-supported treadmill training in persons with an incomplete spinal cord injury improved blood glucose regulation by increasing oxidation and storage of an oral glucose load. Increases in the capacity for transport and phosphorylation glucose in skeletal muscle likely play a role in these adaptations. 相似文献
100.
In 1988 and 1989 a plot containing 668 sunflower plants (cv. Sunbred 246) was inoculated with similar amounts of sclerotia of Sclerotinia sclerotiorum in February or March and disease development was monitored on each plant during the summer. The concentration of airborne ascospores in the plots was measured and was found to correspond to the number of apothecia. In both years ascospore production started early in June and in 1988 reached a peak in mid-July and lasted until the beginning of August. However, in 1989 ascospore production only lasted for about two weeks and airborne concentrations were small. Ascospores were released predominantly during the day, mostly around 1200 BST. Disease symptoms were not observed until July, between 25 and 40 days after ascospores were first found. Disease incidence increased roughly linearly with time until mid-August when the rate of infection declined. In 1988 the number of plants per week with new symptoms was roughly proportional to the average ascospore concentration measured 5 weeks previously. The observations suggest that severity of disease may be related to ascospore concentration during the infection period. 相似文献