全文获取类型
收费全文 | 935篇 |
免费 | 82篇 |
国内免费 | 293篇 |
专业分类
1310篇 |
出版年
2024年 | 5篇 |
2023年 | 15篇 |
2022年 | 44篇 |
2021年 | 48篇 |
2020年 | 48篇 |
2019年 | 45篇 |
2018年 | 30篇 |
2017年 | 33篇 |
2016年 | 40篇 |
2015年 | 43篇 |
2014年 | 57篇 |
2013年 | 77篇 |
2012年 | 84篇 |
2011年 | 101篇 |
2010年 | 72篇 |
2009年 | 55篇 |
2008年 | 68篇 |
2007年 | 59篇 |
2006年 | 63篇 |
2005年 | 51篇 |
2004年 | 37篇 |
2003年 | 44篇 |
2002年 | 44篇 |
2001年 | 42篇 |
2000年 | 24篇 |
1999年 | 11篇 |
1998年 | 13篇 |
1997年 | 12篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 1篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1943年 | 1篇 |
排序方式: 共有1310条查询结果,搜索用时 15 毫秒
921.
922.
Vibha Oza Susan Ashwell Patrick Brassil Jason Breed Chun Deng Jay Ezhuthachan Heather Haye Candice Horn James Janetka Paul Lyne Nicholas Newcombe Ludo Otterbien Martin Pass Jon Read Sian Roswell Mei Su Dorin Toader Dingwei Yu Yan Yu Anna Valentine Xiaolan Zheng 《Bioorganic & medicinal chemistry letters》2010,20(17):5133-5138
Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ’s) was identified by high throughput screening. The optimization of these hits to provide a lead series is described. 相似文献
923.
Neil Bate Christos G. Savva Peter C. E. Moody Edward A. Brown Sian E. Evans Jonathan K. Ball John W. R. Schwabe Julian E. Sale Nicholas P. J. Brindle 《PLoS pathogens》2022,18(7)
Emerging SARS-CoV-2 variants are creating major challenges in the ongoing COVID-19 pandemic. Being able to predict mutations that could arise in SARS-CoV-2 leading to increased transmissibility or immune evasion would be extremely valuable in development of broad-acting therapeutics and vaccines, and prioritising viral monitoring and containment. Here we use in vitro evolution to seek mutations in SARS-CoV-2 receptor binding domain (RBD) that would substantially increase binding to ACE2. We find a double mutation, S477N and Q498H, that increases affinity of RBD for ACE2 by 6.5-fold. This affinity gain is largely driven by the Q498H mutation. We determine the structure of the mutant-RBD:ACE2 complex by cryo-electron microscopy to reveal the mechanism for increased affinity. Addition of Q498H to SARS-CoV-2 RBD variants is found to boost binding affinity of the variants for human ACE2 and confer a new ability to bind rat ACE2 with high affinity. Surprisingly however, in the presence of the common N501Y mutation, Q498H inhibits binding, due to a clash between H498 and Y501 side chains. To achieve an intermolecular bonding network, affinity gain and cross-species binding similar to Q498H alone, RBD variants with the N501Y mutation must acquire instead the related Q498R mutation. Thus, SARS-CoV-2 RBD can access large affinity gains and cross-species binding via two alternative mutational routes involving Q498, with route selection determined by whether a variant already has the N501Y mutation. These mutations are now appearing in emerging SARS-CoV-2 variants where they have the potential to influence human-to-human and cross-species transmission. 相似文献
924.
广西主要森林植被碳储量及其影响因素 总被引:5,自引:0,他引:5
广西森林面积和覆盖率位居全国前列,在全国和区域碳平衡中起着至关重要的作用。正确评价广西森林植被碳储量、碳储量的时空格局及其影响因素对我国碳循环及碳汇研究具有十分重要的意义。为阐明广西森林植被碳储量分布格局及其主要影响因素,基于广西10类主要森林类型345个样地的调查,结合森林资源清查资料,估算广西主要森林植被碳储量,探讨广西不同森林类型、不同龄组、不同层次的碳储量组成与分配。采用地统计学方法描绘了植被碳密度空间分布,并采用主成分分析方法和回归分析方法分析了植被碳储量的影响因素。结果表明:广西主要森林植被总碳储量达到746.06 Tg(1Tg=10~(12) g),平均碳密度为55.37 t/hm~2,松树、杉木、桉树、栎类、软阔、硬阔、石山林、竹林、八角和油茶林对广西植被碳储量的贡献比例分别为26.83%、12.28%、6.67%、3.03%、20.37%、16.32%、10.84%、0.88%、1.38%和1.39%。各森林类型植被碳密度介于20.77—108.28 t/hm~2,大小顺序为硬阔软阔松树杉木栎类石山林桉树八角竹林油茶。广西区森林植被碳密度在7.05—219.73 t/hm~2之间,总体表现为广西北部、西南部和广西东部存在高值区,广西中部和东南部有明显的低值区。碳储量以乔木层占优势,且随林龄增大呈逐渐增加的趋势。影响广西植被碳储量的主控因子是平均胸径、林龄和林分密度,经度、碱解氮、全氮、有机碳是影响碳储量的关键因子。 相似文献
925.
Pseudomonas putida DLL-1是一株甲基对硫磷(MP)高效降解菌株,同时对MP具有趋化性。cheA基因是菌株趋化信号转导过程中负责编码组氨酸激酶的基因,为了研究菌株趋化性在农药原位降解中的作用,通过基因打靶的方式使P.putida DLL-1染色体上单拷贝的cheA基因失活,成功地获得了MP的趋化突变株P.putida DAK,突变株与野生菌株生长能力没有显著差异。通过土壤盆钵试验(MP浓度为50mg/kg),发现在灭菌与未灭菌土壤中趋化突变株对MP的降解能力低于原始出发菌株DLL-1约20%~30%,说明菌株DLL-1趋化性的丧失会减慢其对农药的降解,趋化性在农药的原位降解过程中发挥重要作用。 相似文献
926.
Lauren A. Callender Elizabeth C. Carroll Emilia A. Bober Arne N. Akbar Egle Solito Sian M. Henson 《Aging cell》2020,19(2)
The susceptibility of human CD4+ and CD8+ T cells to senesce differs, with CD8+ T cells acquiring an immunosenescent phenotype faster than the CD4+ T cell compartment. We show here that it is the inherent difference in mitochondrial content that drives this phenotype, with senescent human CD4+ T cells displaying a higher mitochondrial mass. The loss of mitochondria in the senescent human CD8+ T cells has knock‐on consequences for nutrient usage, metabolism and function. Senescent CD4+ T cells uptake more lipid and glucose than their CD8+ counterparts, leading to a greater metabolic versatility engaging either an oxidative or a glycolytic metabolism. The enhanced metabolic advantage of senescent CD4+ T cells allows for more proliferation and migration than observed in the senescent CD8+ subset. Mitochondrial dysfunction has been linked to both cellular senescence and aging; however, it is still unclear whether mitochondria play a causal role in senescence. Our data show that reducing mitochondrial function in human CD4+ T cells, through the addition of low‐dose rotenone, causes the generation of a CD4+ T cell with a CD8+‐like phenotype. Therefore, we wish to propose that it is the inherent metabolic stability that governs the susceptibility to an immunosenescent phenotype. 相似文献
927.
Di Mitri D Azevedo RI Henson SM Libri V Riddell NE Macaulay R Kipling D Soares MV Battistini L Akbar AN 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(5):2093-2100
Persistent viral infections and inflammatory syndromes induce the accumulation of T cells with characteristics of terminal differentiation or senescence. However, the mechanism that regulates the end-stage differentiation of these cells is unclear. Human CD4(+) effector memory (EM) T cells (CD27(-)CD45RA(-)) and also EM T cells that re-express CD45RA (CD27(-)CD45RA(+); EMRA) have many characteristics of end-stage differentiation. These include the expression of surface KLRG1 and CD57, reduced replicative capacity, decreased survival, and high expression of nuclear γH2AX after TCR activation. A paradoxical observation was that although CD4(+) EMRA T cells exhibit defective telomerase activity after activation, they have significantly longer telomeres than central memory (CM)-like (CD27(+)CD45RA(-)) and EM (CD27(-)CD45RA(-)) CD4(+) T cells. This suggested that telomerase activity was actively inhibited in this population. Because proinflammatory cytokines such as TNF-α inhibited telomerase activity in T cells via a p38 MAPK pathway, we investigated the involvement of p38 signaling in CD4(+) EMRA T cells. We found that the expression of both total and phosphorylated p38 was highest in the EM and EMRA compared with that of other CD4(+) T cell subsets. Furthermore, the inhibition of p38 signaling, especially in CD4(+) EMRA T cells, significantly enhanced their telomerase activity and survival after TCR activation. Thus, activation of the p38 MAPK pathway is directly involved in certain senescence characteristics of highly differentiated CD4(+) T cells. In particular, CD4(+) EMRA T cells have features of telomere-independent senescence that are regulated by active cell signaling pathways that are reversible. 相似文献
928.
目的探讨广西忻城县混和痔患者的临床特点。方法将2015年1月~2016年12月在我院诊治的546例混合痔患者的临床资料进行回顾性分析。结果 546例患者中,男248例(45.42%),女298例(54.58%),髙发年龄在31~50岁,饮食诱因以辛辣饮食(253/46.37%)和饮酒(196/35.90%)多见,生活诱因以缺乏运动(205/37.55%)和生活不规律(166/30.40%)多见,排便时间5min 436例(79.85%),主要症状以便血(491/89.93%)和肿物脱出(459/84.07%)为主;中医证型以湿热下注(451/82.60%)为主,主要中医体质类型为湿热质(268/49.08%)和痰湿质(128/23.44%)。结论广西忻城县混合痔患者发病与年龄、饮食、运动、生活、排便时间有关系,证型以湿热下注为主,主要中医体质类型为湿热质和痰湿质。 相似文献
929.
油脂下脚料中残油微生物降解初步研究 总被引:1,自引:0,他引:1
以油脂降解菌Bacillus sp DE-8为出发菌,对油脂下脚料中的残油生物降解条件进行初步研究。结果表明:该菌对油脂下脚料降解条件为:起始pH值为8,接种量4%、摇床转速为150r.min-1、温度为32℃、发酵72h,该菌株对菜籽饼的降解率可达78.8%。 相似文献
930.
镉胁迫对小报春幼苗生长及生理特性的影响 总被引:2,自引:0,他引:2
该研究采用盆栽控制试验,测定不同浓度(0、5、50、100、150、200 mg/kg)土壤Cd胁迫下小报春幼苗生长及生理生化指标,以探究小报春(Primula forbesii Franch.)对重金属镉(Cd)污染的抗性和敏感性,为新型香花地被植物应用于Cd污染土壤提供理论依据。结果表明:(1)低浓度(5 mg/kg)Cd胁迫能促进小报春株高和根长的伸长,高浓度(≥150 mg/kg)Cd胁迫下株高、根长和生物量明显降低。(2)随Cd胁迫浓度增加,小报春幼苗叶片光合作用、叶绿素含量、SOD和CAT活性先上升后下降,而其超氧阴离子产生速率、过氧化氢、丙二醛含量、叶相对电导率和POD活性持续升高。(3)在Cd胁迫条件下,小报春体内K、Zn含量降低,叶和根中Ca、Mg含量显著增加,体内Cd含量明显升高,且根系Cd含量远远高于叶和叶柄。研究发现,小报春幼苗对Cd胁迫具有一定的耐性,低浓度(5 mg/kg)Cd胁迫对小报春生长影响较小,但高浓度(≥150 mg/kg)Cd胁迫对小报春产生明显的毒害作用,影响其正常生长;小报春可能通过增强体内抗氧化酶系统活性、增加叶和根中Ca、Mg含量和根系截留镉来减轻镉胁迫的伤害,提高自身耐受镉胁迫能力。 相似文献