全文获取类型
收费全文 | 7203篇 |
免费 | 723篇 |
国内免费 | 708篇 |
专业分类
8634篇 |
出版年
2024年 | 24篇 |
2023年 | 81篇 |
2022年 | 226篇 |
2021年 | 343篇 |
2020年 | 247篇 |
2019年 | 288篇 |
2018年 | 285篇 |
2017年 | 237篇 |
2016年 | 292篇 |
2015年 | 443篇 |
2014年 | 540篇 |
2013年 | 578篇 |
2012年 | 638篇 |
2011年 | 515篇 |
2010年 | 328篇 |
2009年 | 303篇 |
2008年 | 371篇 |
2007年 | 332篇 |
2006年 | 308篇 |
2005年 | 266篇 |
2004年 | 267篇 |
2003年 | 216篇 |
2002年 | 253篇 |
2001年 | 194篇 |
2000年 | 165篇 |
1999年 | 140篇 |
1998年 | 128篇 |
1997年 | 96篇 |
1996年 | 82篇 |
1995年 | 75篇 |
1994年 | 65篇 |
1993年 | 50篇 |
1992年 | 51篇 |
1991年 | 39篇 |
1990年 | 26篇 |
1989年 | 19篇 |
1988年 | 27篇 |
1987年 | 21篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 30篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1975年 | 1篇 |
1971年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有8634条查询结果,搜索用时 15 毫秒
51.
Inhibition of CLIC4 enhances autophagy and triggers mitochondrial and ER stress-induced apoptosis in human glioma U251 cells under starvation 总被引:1,自引:0,他引:1
CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to mitochondria, endoplasmic reticulum (ER), nucleus and cytoplasm, and participates in the apoptotic response to stress. Apoptosis and autophagy, the main types of the programmed cell death, seem interconnected under certain stress conditions. However, the role of CLIC4 in autophagy regulation has yet to be determined. In this study, we demonstrate upregulation and nuclear translocation of the CLIC4 protein following starvation in U251 cells. CLIC4 siRNA transfection enhanced autophagy with increased LC3-II protein and puncta accumulation in U251 cells under starvation conditions. In that condition, the interaction of the 14-3-3 epsilon isoform with CLIC4 was abolished and resulted in Beclin 1 overactivation, which further activated autophagy. Moreover, inhibiting the expression of CLIC4 triggered both mitochondrial apoptosis involved in Bax/Bcl-2 and cytochrome c release under starvation and endoplasmic reticulum stress-induced apoptosis with CHOP and caspase-4 upregulation. These results demonstrate that CLIC4 nuclear translocation is an integral part of the cellular response to starvation. Inhibiting the expression of CLIC4 enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation. 相似文献
52.
Wang Y Kang G Liu J Zhao M Wu J Zhang X Li Y Zhong X Yang Y Peng S 《Metallomics : integrated biometal science》2012,4(5):441-447
To discover whether novel anti-tumor platinum agents are capable of selectively accumulating in tumor tissue, three novel potassium N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxylhex-1-yl]-L-amino acid dichloroplatinates(II) were prepared. At a dose of 1.67 μmol kg(-1) the in vivo anti-tumor potencies of two of the compounds were higher than that of oxaliplatin. The mortality analysis indicated that these compounds resulted in a 100% survival rate, whereas oxaliplatin lead to an 80% survival rate. The organ damage examination indicated that these compounds induced less damage than oxaliplatin. The platinum accumulation in the organs, blood and bone was significantly lower than that of oxaliplatin treated mice, while the platinum accumulation in the tumor tissue was significantly higher than that of the oxaliplatin treated mice. 相似文献
53.
Despite the importance of stem cells in plant and animal development, the common mechanisms of stem cell maintenance in both systems have remained elusive. Recently, the importance of hydrogen peroxide (H2O2) signaling in priming stem cell differentiation has been extensively studied in animals. Here, we show that different forms of reactive oxygen species (ROS) have antagonistic roles in plant stem cell regulation, which were established by distinct spatiotemporal patterns of ROS‐metabolizing enzymes. The superoxide anion () is markedly enriched in stem cells to activate WUSCHEL and maintain stemness, whereas H2O2 is more abundant in the differentiating peripheral zone to promote stem cell differentiation. Moreover, H2O2 negatively regulates biosynthesis in stem cells, and increasing H2O2 levels or scavenging leads to the termination of stem cells. Our results provide a mechanistic framework for ROS‐mediated control of plant stem cell fate and demonstrate that the balance between and H2O2 is key to stem cell maintenance and differentiation. 相似文献
54.
Solar Cells: Synergic Interface Optimization with Green Solvent Engineering in Mixed Perovskite Solar Cells (Adv. Energy Mater. 20/2017) 下载免费PDF全文
55.
Rong Li Di‐Dong Xie Jun‐hong Dong Hui Li Kang‐shuai Li Jing Su Lai‐Zhong Chen Yun‐Fei Xu Hong‐Mei Wang Zheng Gong Guo‐Ying Cui Xiao Yu Kai Wang Wei Yao Tao Xin Min‐Yong Li Kun‐Hong Xiao Xiao‐fei An Yuqing Huo Zhi‐gang Xu Jin‐Peng Sun Qi Pang 《Journal of neurochemistry》2014,128(2):315-329
Striatal‐enriched tyrosine phosphatase (STEP) is an important regulator of neuronal synaptic plasticity, and its abnormal level or activity contributes to cognitive disorders. One crucial downstream effector and direct substrate of STEP is extracellular signal‐regulated protein kinase (ERK), which has important functions in spine stabilisation and action potential transmission. The inhibition of STEP activity toward phospho‐ERK has the potential to treat neuronal diseases, but the detailed mechanism underlying the dephosphorylation of phospho‐ERK by STEP is not known. Therefore, we examined STEP activity toward para‐nitrophenyl phosphate, phospho‐tyrosine‐containing peptides, and the full‐length phospho‐ERK protein using STEP mutants with different structural features. STEP was found to be a highly efficient ERK tyrosine phosphatase that required both its N‐terminal regulatory region and key residues in its active site. Specifically, both kinase interaction motif (KIM) and kinase‐specific sequence of STEP were required for ERK interaction. In addition to the N‐terminal kinase‐specific sequence region, S245, hydrophobic residues L249/L251, and basic residues R242/R243 located in the KIM region were important in controlling STEP activity toward phospho‐ERK. Further kinetic experiments revealed subtle structural differences between STEP and HePTP that affected the interactions of their KIMs with ERK. Moreover, STEP recognised specific positions of a phospho‐ERK peptide sequence through its active site, and the contact of STEP F311 with phospho‐ERK V205 and T207 were crucial interactions. Taken together, our results not only provide the information for interactions between ERK and STEP, but will also help in the development of specific strategies to target STEP‐ERK recognition, which could serve as a potential therapy for neurological disorders.
56.
57.
Wen-Jie Mu Wen-Jing Zhong Ji-Yi Yao Lu-Jing Li Yu-lan Peng Yi Wang Li-sha Liu Ying Xiao Shou-jun Liu Chang-jun Wu Yu-xin Jiang Shyam Sundar Parajuly Ping Xu Yi Hao Jing Li Bao-Ming Luo Hui Zhi 《PloS one》2016,11(2)
Background
This study aimed to confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating benign and malignant breast lesions on ultrasonographic elastography(UE).Materials and Methods
From June 2010 to March 2012, 1080 consecutive female patients with breast lesions were recruited into a multicenter retrospective study, which involved 8 centers across China. Each institutional ethic review board approved the study, and all the patients gave written informed consent. All the patients underwent the UE procedure and the strain ratios were calculated and the final diagnosis was made by histological findings. The sensitivity, specificity, accuracy, PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared.Results
The strain ratios of benign lesions (mean, 2.6±2.0) and malignant lesions (mean,7.9±5.8) were significantly different (p <0.01). When the cutoff point was 3.01, strain ratio method had 79.8% sensitivity, 82.8% specificity, and 81.3% accuracy, while the 5-point scoring method had 93.1% sensitivity, 73.0% specificity, and 76.8% accuracy. The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.863 and 0.865, respectively(p>0.05). The strain ratio method shows better a diagnosis performance of the lesions with elasticity score 3 and 4.Conclusions
Although the two UE methods have similar diagnostic performance, separate calculation of the strain ratios seems compulsory, especially for the large solid breast lesions and the lesions with elasticity score 3 and 4. 相似文献58.
本文报道了棉铃虫单粒包埋型核型多角体病毒(Heliothis armigera single nucleocapsid nuclear polyhedrosis virus, HaSNPV)在棉铃虫及棉铃虫蛹卵巢细胞系SFE-HA-8212中的复制。HaSNPV的复制和其他的核型多角体病毒大体相符,复制过程也可分为形成出芽型病毒与形成包埋型病毒这两个时相。研究了影响病毒在细胞中复制的诸因素,包括病毒感染复数、细胞接种密度和细胞生长阶段等。在适宜的条件下平均每细胞可生产出芽型病毒14PFU,多角体24个。生成的病毒具有感染力。这些表明SFE-HA-8212细胞可供HaSNPV有效复制。同时,作为细胞群体该细胞系对HaSNPV感染的反应并非均一,其中有89.65±21.4%的感染细胞释放病毒,但仅有37.85±6.7%的细胞形成多角体。表明HaSNPV的感染并不一定导致形成多角体,在大部分感染细胞中病毒复制进行到产生病毒粒子就停止了。初步讨论了这种不均一性的原因。 相似文献
59.
Induction of multiple cytotoxic T lymphocyte responses in mice by a multiepitope DNA vaccine against dengue virus serotype 1 下载免费PDF全文
Xin Yu Chen De Zhou Li Xiao Zhi Zhong Bokun Chen Zhi Liang Duan Jin Sheng Wen 《Microbiology and immunology》2016,60(12):835-845
60.
在黄花蒿(Artemisia annua L.)发根液体培养中,黄花蒿内生炭疽菌(Colletotrichum sp. B501)细胞壁寡糖提取物可促进发根青蒿素的合成.经寡糖诱导子(20 mg/L)处理4 d后,发根青蒿素含量达1.15 mg/g, 比对照高出64.29%.诱导作用与诱导子浓度、作用时间相关.诱导处理1 d后,X射线能谱分析表明黄花蒿发根细胞中Ca2+积累量显著增高,电镜观察发现液泡内出现高电子致密物,具活性氧清除作用的过氧化物酶表现出高活性(6.5 unit*min-1*g-1 FW).诱导处理第三天,细胞核DNA呈梯度条带降解,部分细胞出现程序化死亡.内生菌细胞壁寡糖提取物引起的生理反应有利于细胞中青蒿素的生物合成. 相似文献