全文获取类型
收费全文 | 2868篇 |
免费 | 267篇 |
国内免费 | 461篇 |
出版年
2024年 | 6篇 |
2023年 | 53篇 |
2022年 | 82篇 |
2021年 | 229篇 |
2020年 | 179篇 |
2019年 | 190篇 |
2018年 | 177篇 |
2017年 | 134篇 |
2016年 | 168篇 |
2015年 | 254篇 |
2014年 | 261篇 |
2013年 | 257篇 |
2012年 | 289篇 |
2011年 | 253篇 |
2010年 | 143篇 |
2009年 | 126篇 |
2008年 | 132篇 |
2007年 | 106篇 |
2006年 | 92篇 |
2005年 | 79篇 |
2004年 | 44篇 |
2003年 | 49篇 |
2002年 | 44篇 |
2001年 | 26篇 |
2000年 | 24篇 |
1999年 | 25篇 |
1998年 | 20篇 |
1997年 | 25篇 |
1996年 | 26篇 |
1995年 | 11篇 |
1994年 | 13篇 |
1993年 | 3篇 |
1992年 | 10篇 |
1991年 | 15篇 |
1990年 | 12篇 |
1989年 | 11篇 |
1988年 | 9篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 1篇 |
排序方式: 共有3596条查询结果,搜索用时 31 毫秒
101.
Xiaojing Tong Peng Mu Yuhua Zhang Jiao Zhao Xiaobin Wang 《Journal of cellular physiology》2020,235(11):8236-8245
Tripartite motif containing 59 (TRIM59) functions as an oncoprotein in various human cancers including ovarian cancer. In this study, we found that TRIM59 gene amplification was prevalent in ovarian cancer tissues, and its amplification was significantly correlated with poorer overall survival. Moreover, knockdown of TRIM59 in SKOV3 and OVCAR3 cells, which had relatively high level of TRIM59, suppressed glucose uptake and lactate production. TRIM59 knockdown also decreased the expression of c-Myc and lactate dehydrogenase A, and the phosphorylation of extracellular signal-regulated kinase (ERK). TRIM59 overexpression in A2780 cells, which expressed low level of TRIM59, showed reverse effects. Notably, treatment with an ERK inhibitor (PD98059) completely abolished the oncogenic effects of TRIM59 overexpression. Interestingly, TRIM59 increased the ubiquitination of MAP kinase phosphatase 3 (MKP3), which may dephosphorylate and inactivate ERK. Ectopic expression of MKP3 inhibited the promoting effects of TRIM59 on glycolysis and the phosphorylation of ERK. TRIM59 protein expression was negatively correlated with MKP3 protein expression in ovarian cancer tissues. Finally, TRIM59 amplification potently affected the anticancer effect of 3-bromopyruvate, an inhibitor of glycolysis, in ovarian cancer cells and patient-derived xenograft. In conclusion, these results suggest that TRIM59 may regulate glycolysis in ovarian cancer via the MKP3/ERK pathway. 相似文献
102.
Jiamao Fan Qing Zhu Zhenhua Wu Jiao Ding Shuai Qin Hui Liu Pengfei Miao 《Journal of cellular physiology》2020,235(2):1165-1174
Recent evidence has verified the cardioprotective actions of irisin in different diseases models. However, the beneficial action of irisin on hypoxia-reoxygenation (HR) injury under high glucose stress has not been described. Herein our research investigated the influence of irisin on HR-triggered cardiomyocyte death under high glucose stress. HR model was established in vitro under high glucose treatment. The results illuminated that HR injury augmented apoptotic ratio of cardiomyocyte under high glucose stress; this effect could be abolished by irisin via modulating mitochondrial function. Irisin treatment attenuated cellular redox stress, improved cellular ATP biogenetics, sustained mitochondria potential, and impaired mitochondrion-related cell death. At the molecular levels, irisin treatment activated the 5′-adenosine monophosphate-activated protein kinase (AMPK) pathway and the latter protected cardiomyocyte and mitochondria against HR injury under high glucose stress. Altogether, our results indicated a novel role of irisin in HR-treated cardiomyocyte under high glucose stress. Irisin-activated AMPK pathway and the latter sustained cardiomyocyte viability and mitochondrial function. 相似文献
103.
球虫病给养禽业带来巨大经济损失,人们对绿色健康食品的迫切需求使球虫病的防控面临新的挑战。伴随世界"禁抗"进程的不断推进,家禽养殖业亟需一种安全有效的新型抗球虫方法。益生菌可竞争性排斥病原菌定殖以防止球虫病继发感染,可刺激宿主抗菌肽、黏蛋白和紧密连接蛋白的分泌以抵御球虫入侵,还可激活免疫反应以增强机体抗球虫感染的能力。本文从调控肠道微生物群、改善肠黏膜屏障和调节免疫系统功能等方面综述了益生菌在预防和控制家禽球虫病中的作用,以期为高效抗球虫益生菌制剂的研发提供参考。 相似文献
104.
[目的] 从医院污水中分离金黄色葡萄球菌噬菌体,观察其形态,确证裂解谱特征并研究生物学和基因学特性,为噬菌体的临床应用奠定实验基础。[方法] 将金黄色葡萄球菌ATCC25923作为宿主菌,采用双层琼脂平板法从医院污水中分离纯化噬菌体,电镜下观察形态并测定其最佳感染复数、一步生长曲线及裂解谱;全基因组测序并进行基因结构分析和功能注释。[结果] 从4份医院污水中共分离到1株金黄色葡萄球菌噬菌体(命名为vB_SauH_SAP1),仅裂解10株临床分离的葡萄球菌属受试菌(共计37株),其余74株其他种属菌株不能被裂解;透射电镜观察具有正20面体头部和收缩性尾部,属于肌尾噬菌体;其最佳感染复数为0.1,潜伏期10 min,裂解期为20 min。vB_SauH_SAP1基因组全长143375 bp,G+C含量为30.2%,编码226个开放阅读框(ORF),未发现已知的毒力相关基因和抗生素抗性基因,基因组与Kayvirus属葡萄球菌噬菌体有较高的同源性。[结论] 分离到1株新的Kayvirus属金黄色葡萄球菌噬菌体,根据生物学特性和基因组研究,具有一定的潜在应用价值。 相似文献
105.
Yuanqing Hu Yuwei Shang Jinlin Huang Yan Wang Fangzhe Ren Yang Jiao Zhiming Pan Xin-an Jiao 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Campylobacter jejuni is an important food-borne and zoonotic pathogen with a worldwide distribution. Humans and chickens are hosts of this pathogen. At present, there is no ideal vaccine for controlling human campylobacteriosis or the carriage of C. jejuni by chickens. Bacterial in vivo-induced antigens are useful as potential vaccine candidates and biomarkers of virulence.Methods
In this study, we developed a novel systematic immunoproteomics approach to identify in vivo-induced antigens among the total cell proteins of C. jejuni using pre-adsorbed sera from patients infected with C. jejuni.Results
Overall, 14 immunoreactive spots were probed on a PVDF membrane using pre-adsorbed human sera against C. jejuni. Then, we excised these protein spots from a duplicate gel and identified using MALDI–TOF MS. In total, 14 in vivo-induced antigens were identified using PMF and BLAST analysis. The identified proteins include CadF (CadF-1 and CadF-2), CheW, TufB, DnaK, MetK, LpxB, HslU, DmsA, PorA, ProS, CJBH_0976, CSU_0396 and hypothetical protein cje135_05017. Real-time RT-PCR was performed on 9 genes to compare their expression levels in vivo and in vitro. The data showed that 8 of the 9 analyzed genes were significantly upregulated in vivo relative to in vitro.Conclusion
We successfully developed a novel immunoproteomics method for identifying in vivo-induced Campylobacter jejuni antigens by using pre-adsorbed sera from infected patients.General significance
This new analysis method may prove to be useful for identifying in vivo-induced antigens within any host infected by bacteria and will contribute to the development of new subunit vaccines. 相似文献106.
Wenjing Song Huwei Sun Jiao Li Xianpo Gong Shuangjie Huang Xudong Zhu Yali Zhang Guohua Xu 《Annals of botany》2013,112(7):1383-1393
Background and Aims
Although ammonium (NH4+) is the preferred form of nitrogen over nitrate (NO3−) for rice (Oryza sativa), lateral root (LR) growth in roots is enhanced by partial NO3− nutrition (PNN). The roles of auxin distribution and polar transport in LR formation in response to localized NO3− availability are not known.Methods
Time-course studies in a split-root experimental system were used to investigate LR development patterns, auxin distribution, polar auxin transport and expression of auxin transporter genes in LR zones in response to localized PNN in ‘Nanguang’ and ‘Elio’ rice cultivars, which show high and low responsiveness to NO3−, respectively. Patterns of auxin distribution and the effects of polar auxin transport inhibitors were also examined in DR5::GUS transgenic plants.Key Results
Initiation of LRs was enhanced by PNN after 7 d cultivation in ‘Nanguang’ but not in ‘Elio’. Auxin concentration in the roots of ‘Nanguang’ increased by approx. 24 % after 5 d cultivation with PNN compared with NH4+ as the sole nitrogen source, but no difference was observed in ‘Elio’. More auxin flux into the LR zone in ‘Nanguang’ roots was observed in response to NO3− compared with NH4+ treatment. A greater number of auxin influx and efflux transporter genes showed increased expression in the LR zone in response to PNN in ‘Nanguang’ than in ‘Elio’.Conclusions
The results indicate that higher NO3− responsiveness is associated with greater auxin accumulation in the LR zone and is strongly related to a higher rate of LR initiation in the cultivar ‘Nanguang’. 相似文献107.
108.
109.
Jianhua Cao Jiao Yang Youhua Wang Jian Xu Zhengming Zhou Chun Cheng Xiaojuan Liu Xinghai Cheng Long Long Xingxing Gu 《Cellular and molecular neurobiology》2013,33(2):213-221
As a novel cell cycle protein, Spy1 enhances cell proliferation, promotes the G1/S transition as well as inhibits apoptosis in response to UV irradiation. Spy1 levels are tightly regulated during mammary development, and overexpression of Spy1 accelerates tumorigenesis in vivo. But little is known about the role of Spy1 in the pathological process of damage and regeneration of the peripheral nervous system. Here we established a rat sciatic nerve crush (SNC) model to examine the spatiotemporal expression of Spy1. Spy1 expression was elevated gradually after sciatic nerve crush and peaked at day 3. The alteration was due to the increased expression of Spy1 in axons and Schwann cells after SNC. Spy1 expression correlated closely with Schwann cells proliferation in sciatic nerve post injury. Furthermore, Spy1 largely localized in axons in the crushed segment, but rarely co-localized with GAP43. These findings suggested that Spy1 participated in the pathological process response to sciatic nerve injury and may be associated with Schwann cells proliferation and axons regeneration. 相似文献
110.
Zhong Chen Qi Qian Chengchun Tang Jiandong Ding Yi Feng Genshan Ma 《Molecular biology reports》2013,40(2):1021-1026
Two novel single nucleotide polymorphisms (SNPs; rs7529229 and rs2228145) in the interleukin-6 receptor (IL6R) gene have recently been associated with coronary heart disease (CHD) in a European population. We sought to replicate this finding and to investigate associations of these two SNPs with the severity and clinical phenotypes of premature CHD in a Chinese Han population. A total of 418 patients were studied, including 187 cases with coronary stenosis ≥50 % or acute myocardial infarction (males < 55 years and females < 65 years) and 231 controls without documented CHD. A ligase detection reaction was performed to detect rs7529229 and rs2228145. There were no differences between the controls and premature CHD groups in the frequencies for the three genotypes and alleles of rs7529229 and rs2228145 (all P > 0.05), nor did they differ between the two groups when grouped by gender (all P > 0.05). There were also no associations between these two SNPs and the severity of coronary lesions or clinical phenotypes of premature CHD (all P > 0.05). Our results do not support an association between rs7529229 or rs2228145 with premature CHD in the Chinese Han population. Further studies are warranted to elucidate the role of these two SNPs in the development of atherosclerosis and CHD. 相似文献