首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   4569篇
  免费   352篇
  国内免费   561篇
  5482篇
  2024年   14篇
  2023年   62篇
  2022年   189篇
  2021年   286篇
  2020年   207篇
  2019年   243篇
  2018年   227篇
  2017年   171篇
  2016年   247篇
  2015年   329篇
  2014年   428篇
  2013年   374篇
  2012年   482篇
  2011年   434篇
  2010年   287篇
  2009年   243篇
  2008年   275篇
  2007年   219篇
  2006年   140篇
  2005年   146篇
  2004年   91篇
  2003年   87篇
  2002年   50篇
  2001年   38篇
  2000年   29篇
  1999年   19篇
  1998年   10篇
  1997年   10篇
  1996年   7篇
  1995年   8篇
  1994年   6篇
  1993年   3篇
  1992年   12篇
  1991年   9篇
  1990年   9篇
  1989年   12篇
  1988年   5篇
  1987年   8篇
  1986年   12篇
  1985年   11篇
  1984年   5篇
  1983年   8篇
  1982年   3篇
  1980年   7篇
  1978年   4篇
  1974年   2篇
  1973年   3篇
  1972年   2篇
  1965年   1篇
  1956年   1篇
排序方式: 共有5482条查询结果,搜索用时 15 毫秒
1.
International hospital-based studies have indicated a high risk of cognitive impairment after stroke, evidence from community-based studies in China is scarce. To determine the prevalence of post-stroke cognitive impairment (PSCI) and its subtypes in stroke survivors residing in selected rural and urban Chinese communities, we conducted a community-based, cross-sectional study in 599 patients accounting for 48% of all stroke survivors registered in the 4 communities, who had suffered confirmed strokes and had undergone cognitive assessments via the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Hachinski Ischemia Scale (HIS). Detection of PSCI was based on scores in these neuropsychological scales. Factors potentially impacting on occurrence of PSCI were explored by comparing demographic characteristics, stroke features, and cardiovascular risk factors between patients with and without PSCI. The overall prevalence of PSCI was 80.97% (95%CI: 77.82%-84.11%), while that of non-dementia PSCI (PSCI-ND) and post-stroke vascular dementia (PSD) was 48.91% (95%CI: 44.91%-52.92%) and 32.05% (95%CI: 28.32%-35.79%), respectively. Prior stroke and complications during the acute phase were independent risk factors for PSCI. The risk of recurrent stroke survivors having PSCI was 2.7 times higher than for first-episode survivors, and it was 3 times higher for those with complications during the acute phase than for those without. The higher prevalence of PSCI in this study compared with previous Chinese studies was possibly due to the combined effects of including rural stroke survivors, a longer period from stroke onset, and different assessment methods. There is an urgent need to recognize and prevent PSCI in stroke patients, especially those with recurrent stroke and complications during the acute phase.  相似文献   
2.
N,N′-Dicyclohexylcarbodiimide (DCCD) inhibits the activity of ubiquinol-cytochrome c reductase in the isolated and reconstitued mitochondrial cytochrome b-c1 complex. DCCD inhibits equally electron flow and proton translocation (i.e., the H+e? ratio is not affected) catalysed by the enzyme reconstituted into phospholipid vesicles. The inhibitory effects are accompanied by structural alterations in the polypeptide pattern of both isolated and reconstituted enzyme. Cross-linking was observed between subunits V (iron-sulfur protein) and VII, indicating that these polypeptides are in close proximity. A clear correlation was found between the kinetics of inhibition of enzymic activity and the cross-linking, suggesting that the two phenomena may be coupled. Binding of [14C]DCCD was also observed, to all subunits with the isolated enzyme and preferentially to cytochrome b with the reconstituted vesicles; in both cases, however, it was not correlated kinetically with the inhibition of the enzymic activity.  相似文献   
3.
Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.  相似文献   
4.
Five new ent-pimarane diterpenes ( 1 – 5 ) and five known analogs ( 6 – 10 ) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC50 values of 16.35±2.59 and 18.86±4.83 μM, respectively.  相似文献   
5.
赵泽宇  刘娜  邢晓科 《菌物学报》2021,40(3):423-435
兰科植物因其具有丰富的物种多样性和重要的社会经济价值,多年来一直是植物学及生态学界的重点研究对象.菌根真菌对兰科植物的种子萌发、营养吸收和种群动态等多个方面都具有十分重要的作用,因而近年来受到越来越多的关注.探究菌根真菌与兰科植物互作的内在机制是目前兰科菌根研究的一大热点领域,同时也为兰科植物野生资源保护和种群恢复提供...  相似文献   
6.
In plants, recognition of small secreted peptides, such as damage/danger‐associated molecular patterns (DAMPs), regulates diverse processes, including stress and immune responses. Here, we identified an SGPS (Ser‐Gly‐Pro‐Ser) motif‐containing peptide, Nicotiana tabacum NtPROPPI, and its two homologs in Nicotiana benthamiana, NbPROPPI1 and NbPROPPI2. Phytophthora parasitica infection and salicylic acid (SA) treatment induced NbPROPPI1/2 expression. Moreover, SignalP predicted that the 89‐amino acid NtPROPPI includes a 24‐amino acid N‐terminal signal peptide and NbPROPPI1/2‐GFP fusion proteins were mainly localized to the periplasm. Transient expression of NbPROPPI1/2 inhibited P. parasitica colonization, and NbPROPPI1/2 knockdown rendered plants more susceptible to P. parasitica. An eight‐amino‐acid segment in the NbPROPPI1 C‐terminus was essential for its immune function and a synthetic 20‐residue peptide, NbPPI1, derived from the C‐terminus of NbPROPPI1 provoked significant immune responses in N. benthamiana. These responses led to enhanced accumulation of reactive oxygen species, activation of mitogen‐activated protein kinases, and up‐regulation of the defense genes Flg22‐induced receptor‐like kinase (FRK) and WRKY DNA‐binding protein 33 (WRKY33). The NbPPI1‐induced defense responses require Brassinosteroid insensitive 1‐associated receptor kinase 1 (BAK1). These results suggest that NbPPI1 functions as a DAMP in N. benthamiana; this novel DAMP provides a potentially useful target for improving plant resistance to Pytophthora pathogens.  相似文献   
7.
In the devastating rice blast fungus Magnaporthe oryzae, six Magnaporthe appressoria‐specific (MAS) proteins are encoded by MoGAS1, MoGAS2 and MoMAS3MoMAS6. MoGAS1 and MoGAS2 were previously characterized as M. oryzae virulence factors; however, the roles of the other four genes are unknown. Here, we found that, although the loss of any MAS gene did not affect appressorial formation or vegetative growth, ∆Momas3 and ∆Momas5 mutant strains (but not the others) were reduced in virulence on susceptible CO‐39 rice seedlings. Focusing on ∆Momas3 and ∆Momas5 mutant strains, we found that they could penetrate host leaf surfaces and fill the first infected rice cell but did not spread readily to neighbouring cells, suggesting they were impaired for biotrophic growth. Live‐cell imaging of fluorescently labelled MoMas3 and MoMas5 proteins showed that during biotrophy, MoMas3 localized to the apoplastic compartment formed between fungal invasive hyphae and the plant‐derived extra‐invasive hyphal membrane while MoMas5 localized to the appressoria and the penetration peg. The loss of either MoMAS3 or MoMAS5 resulted in the accumulation of reactive oxygen species (ROS) in infected rice cells, resulting in the triggering of plant defences that inhibited mutant growth in planta. ∆Momas3 and ∆Momas5 biotrophic growth could be remediated by inhibiting host NADPH oxidases and suppressing ROS accumulation. Thus, MoMas3 and MoMas5 are novel virulence factors involved in suppressing host plant innate immunity to promote biotrophic growth.  相似文献   
8.
灵芝药品大多以灵芝子实体水提物为原料,为快速准确测定灵芝子实体水提物及相关产品中三萜的含量,建立了具有较好分离效果的HPLC分析测定方法。通过优化色谱柱和洗脱条件,优选出Agilent Zorbax SB-Aq C18色谱柱(250 mm×4.6 mm,5μm),以乙腈-乙酸水溶液(0.01%)为流动相梯度洗脱,流速为1.0 mL/min,检测波长252 nm,柱温30℃,该条件下灵芝酸A、灵芝酸F等10种灵芝酸得到较好的分离。方法学考察显示该分析方法精密度、重复性、稳定性和加样回收率的RSD值均小于5%,可以用于灵芝酸C2、灵芝酸G、灵芝烯酸B、灵芝酸B等10种灵芝酸的定量检测。通过对灵芝子实体原料、水提物和市售灵芝产品中10种三萜类成分分析发现,灵芝子实体水提物中均含有这10种三萜,含量为2.52%–6.83%,较子实体原料大幅提高,市售的灵芝产品中的三萜含量为0.27%–0.84%。该方法的建立为灵芝水提物及其产品质量标准的建立奠定基础。  相似文献   
9.
黄土高原不同树种枯落叶混合分解效应   总被引:2,自引:0,他引:2  
混交林中不同树种枯落物混合分解是否产生促进或抑制作用是评价种间关系和混交适宜性的重要依据之一。以黄土高原主要树种为对象,通过室内枯落叶混合分解模拟试验,结果表明:(1)沙棘、白榆、柠条和小叶杨枯落叶分解最快(周转期1 a左右),其次为旱柳、侧柏和白桦枯落叶(周转期略大于1 a),紫穗槐、辽东栎和刺槐枯落叶分解稍慢(周转期1.5 a左右),而樟子松、落叶松和油松枯落叶分解最慢(周转期略大于2 a)。(2)对于针叶树,与油松枯落叶混合,存在明显促进分解作用的是侧柏、落叶松,其次是白桦、沙棘和刺槐;与樟子松枯落叶混合,存在明显促进分解作用的是落叶松、侧柏、沙棘、白榆,其次是柠条、紫穗槐和小叶杨,而存在明显抑制分解作用的是刺槐,其次是白桦和辽东栎;与落叶松枯落叶混合,存在较明显促进分解作用的是白榆、白桦和辽东栎,存在较明显抑制作用的是刺槐;紫穗槐与侧柏枯落叶混合存在较明显的抑制分解作用。(3)对于阔叶树,与小叶杨枯落叶混合,存在较明显促进分解作用的是紫穗槐,其次是辽东栎和刺槐;与刺槐枯落叶混合,存在较明显促进分解作用的是白榆和沙棘,存在明显抑制分解作用的是柠条,其次是辽东栎和白桦;与白桦枯落叶混合,存在较明显促进分解作用的是辽东栎和紫穗槐,存在较明显抑制分解作用的是柠条;白榆与辽东栎、旱柳枯落叶混合均存在较明显的促进分解作用,而白榆与柠条枯落叶混合存在较明显的抑制分解作用;紫穗槐与旱柳、沙棘枯落叶混合均存在较明显的促进分解作用,而紫穗槐与柠条枯落叶混合有较明显的抑制作用。  相似文献   
10.
砷是一种致癌物,是心血管、外周血管疾病、神经疾病、糖尿病和各种癌症的致病因素。目的:利用GO数据库和KEGG数据库等生物信息学方法对GEO数据库数据中的差异表达基因进行评价。利用生物信息学分析软件对差异基因进行功能富集、功能注释分析和生存分析。利用Cytoscape上的蛋白-蛋白相互作用网络(Protein-protein interaction network, PPI)软件对179个差异基因进行筛选和分析。结果发现126个基因作用于蛋白靶点,其中有10个基因为关键基因分别为:PSMB3、HSP701、HSPE1、STIP1、HSPD1、HSP70、DNAJB1B、HSP90AA1.1、HSPA9H和TCP1。核心基因主要作用于内质网中的蛋白质加工通路。这可能会为砷对肝脏损伤的潜在生物标志物和生物学机制提供新的思路。  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号