全文获取类型
收费全文 | 4459篇 |
免费 | 374篇 |
国内免费 | 418篇 |
专业分类
5251篇 |
出版年
2024年 | 11篇 |
2023年 | 67篇 |
2022年 | 149篇 |
2021年 | 216篇 |
2020年 | 154篇 |
2019年 | 243篇 |
2018年 | 196篇 |
2017年 | 149篇 |
2016年 | 181篇 |
2015年 | 295篇 |
2014年 | 335篇 |
2013年 | 338篇 |
2012年 | 422篇 |
2011年 | 437篇 |
2010年 | 234篇 |
2009年 | 187篇 |
2008年 | 213篇 |
2007年 | 206篇 |
2006年 | 189篇 |
2005年 | 155篇 |
2004年 | 125篇 |
2003年 | 106篇 |
2002年 | 86篇 |
2001年 | 78篇 |
2000年 | 44篇 |
1999年 | 55篇 |
1998年 | 42篇 |
1997年 | 46篇 |
1996年 | 43篇 |
1995年 | 29篇 |
1994年 | 36篇 |
1993年 | 17篇 |
1992年 | 27篇 |
1991年 | 22篇 |
1990年 | 16篇 |
1989年 | 12篇 |
1988年 | 11篇 |
1987年 | 14篇 |
1986年 | 7篇 |
1985年 | 19篇 |
1983年 | 2篇 |
1980年 | 2篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 6篇 |
1971年 | 5篇 |
1970年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有5251条查询结果,搜索用时 15 毫秒
31.
Bo Li YuZhen Ge WeiWei Yan Bin Gong Kun Cao Rui Zhao Chao Li YeWei Zhang YiHeng Jiang Shi Zuo 《Cell proliferation》2022,55(9)
As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic β‐catenin destruction complex (GSK‐3β and Axin), promotes the ubiquitination degradation of β‐catenin, and inhibits its nuclear transfer, thus, decreasing c‐Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.Decreased expression of DNASE1L3 is associated with poor prognosis in patients with HCC DNASE1L3 inhibits the proliferation and cell cycle of HCC cells in vitro and promotes the invasion and metastasis of HCC cells DNASE1L3 inhibits the tumorigenicity and metastasis of HCC cells in vivo DNASE1L3 interacts with β‐catenin and promotes its binding to the β‐catenin destroying complex DNASE1L3 interacts with P21 and stabilizes P21 by mediating the deubiquitin activity 相似文献
32.
BackgroundPlanarian has attracted increasing attentions in the regeneration field for its usefulness as an important biological model organism attributing to its strong regeneration ability. Both the complexity of multiple regulatory networks and their coordinate functions contribute to the maintenance of normal cellular homeostasis and the process of regeneration in planarian. The polarity, size, location and number of regeneration tissues are regulated by diverse mechanisms. In this review we summarize the recent advances about the importance genetic and molecular mechanisms for regeneration control on various tissues in planarian.MethodsA comprehensive literature search of original articles published in recent years was performed in regards to the molecular mechanism of each cell types during the planarian regeneration, including neoblast, nerve system, eye spot, excretory system and epidermal.ResultsAvailable molecular mechanisms gave us an overview of regeneration process in every tissue. The sense of injuries and initiation of regeneration is regulated by diverse genes like follistatin and ERK signaling. The Neoblasts differentiate into tissue progenitors under the regulation of genes such as egfr‐3. The regeneration polarity is controlled by Wnt pathway, BMP pathway and bioelectric signals. The neoblast within the blastema differentiate into desired cell types and regenerate the missing tissues. Those tissue specific genes regulate the tissue progenitor cells to differentiate into desired cell types to complete the regeneration process.ConclusionAll tissue types in planarian participate in the regeneration process regulated by distinct molecular factors and cellular signaling pathways. The neoblasts play vital roles in tissue regeneration and morphology maintenance. These studies provide new insights into the molecular mechanisms for regulating planarian regeneration. Genetic and molecular mechanisms for regeneration control on various tissues in planarian. 相似文献
33.
Yucheng Liu Shulin Liu Zhifang Zhang Lingbin Ni Xingming Chen Yunxia Ge Guoan Zhou Zhixi Tian 《中国科学:生命科学英文版》2022,65(9):1898-1901
<正>Dear Editor,Soybean(Glycine max [L.] Merr.) provides more than half of the oilseeds and more than a quarter of protein worldwide. It is estimated that the production of soybean has to be doubled by 2050 to meet the needs of the rapidly increasing consumption of soybean seeds along with a continuously increasing population(Ray et al., 2013). As such, development of a genotyping platform with high throughput, high efficiency and high precision but low-cost is urgently needed to accelerate... 相似文献
34.
Tianli Zou Junhua Deng Xiangdong Li Shiyin Zhang Lingyan Chen Liying Hao Jinshan Zhuang Heng Wang Guihong Zhang Shengxiang Ge Kegong Tian 《中国病毒学》2022,37(3):462-464
Highlights
1. A probe-based insulated isothermal PCR (iiPCR) assay was developed for rapid and onsite detection of ASFV.
2. The developed iiPCR showed similar sensitivity and specificity with OIE recommended real-time PCR.
3. Blood samples could be directly applied as PCR template in iiPCR without DNA extraction. 相似文献
1. A probe-based insulated isothermal PCR (iiPCR) assay was developed for rapid and onsite detection of ASFV.
2. The developed iiPCR showed similar sensitivity and specificity with OIE recommended real-time PCR.
3. Blood samples could be directly applied as PCR template in iiPCR without DNA extraction. 相似文献
35.
Chang Ge Huakang Sheng Xin Chen Xiaolin Shen Xinxiao Sun Yajun Yan Jia Wang Qipeng Yuan 《Biotechnology journal》2020,15(6)
Quorum sensing (QS) is a ubiquitous cell–cell communication mechanism in microbes that coordinates population‐level cell behaviors, such as biofilm production, virulence, swarming motility, and bacterial persistence. Efforts to engineer QS systems to take part in metabolic network regulation represent a promising strategy for synthetic biology and pathway engineering. Recently, design, construction, and implementation of QS circuits for programmed control of bacterial phenotypes and metabolic pathways have gained much attention, but have not been reviewed recently. In this article, the architectural organizations and genetic contributions of the naturally occurring QS components to understand the mechanisms are summarized. Then, the most recent progress in application of QS toolkits to develop synthetic networks for novel cell behaviors creation and metabolic pathway engineering is highlighted. The current challenges in large‐scale application of these QS circuits in synthetic biology and metabolic engineering fields are discussed and future perspectives for further engineering efforts are provided. 相似文献
36.
MiR‐616‐3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia
下载免费PDF全文
![点击此处可从《Cell proliferation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yetao Xu Dan Wu Ziyan Jiang Yuanyuan Zhang Sailan Wang Zhonghua Ma Bingqing Hui Jing Wang Weiping Qian Zhiping Ge Lizhou Sun 《Cell proliferation》2018,51(5)
Objectives
Despite improvements in diagnosis and treatment, preeclampsia (PE) continues to pose a significant risk of maternal and foetal morbidity and mortality if not addressed promptly. An increasing number of studies have suggested that tissue factor pathway inhibitor 2 (TFPI2) acts as a suppressor gene, possibly inhibiting multiple serine proteases affecting cell proliferation and migration. It plays an essential role in the occurrence and development of PE, but the pathogenesis remains unclear.Materials and methods
In our research, we performed western blotting, immunohistochemistry and qPCR assays to investigate TFPI2 and miR‐616‐3p expression in preeclamptic placental tissues. Cell assays were performed in HTR‐8/SVneo and JEG3 cell lines. Cell proliferation and migration events were investigated by MTT, EdU and transwell assays. In conjunction with bioinformatics analysis, luciferase reporter assays were performed to elucidate the mechanism by which miR‐616‐3p binds to TFPI2 mRNA.Results
We established that TFPI2 protein levels were significantly upregulated in PE placental tissues. In addition, we found that miR‐616‐3p binds specifically to the 3′‐UTR region of TFPI2 mRNA. Furthermore, miR‐616‐3p knockdown or TFPI2 overexpression substantially impaired cell growth and migration, whereas miR‐616‐3p upregulation or TFPI2 knockdown stimulated cell proliferation and migration. This miR‐616‐3p / TFPI2 axis was also found to affect the epithelial‐mesenchymal transition process in PE.Conclusions
Our results demonstrated that TFPI2 plays a vital role in the progression of PE and might provide a prospective therapeutic strategy to mitigate the severity of the disorder.38.
Genetic variation within and among populations of a wild rice Oryza granulata from China detected by RAPD and ISSR markers 总被引:37,自引:0,他引:37
W. Qian S. Ge D.-Y. Hong 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2001,102(2-3):440-449
Genetic variation within and between five populations of Oryza granulata from two regions of China was investigated using RAPD (random amplified polymorphic DNA) and ISSR (inter-simple sequence
repeat amplification) markers. Twenty RAPD primers used in this study amplified 199 reproducible bands with 61 (30.65%) polymorphic;
and 12 ISSR primers amplified 113 bands with 52 (46.02%) polymorphic. Both RAPD and ISSR analyses revealed a low level of
genetic diversity in wild populations of O. granulata. Furthermore, analysis of molecular variance (AMOVA) was used to apportion the variation within and between populations both
within and between regions. As the RAPD markers revealed, 73.85% of the total genetic diversity resided between the two regions,
whereas only 19.45% and 6.70% were present between populations within regions and within a population respectively. Similarly,
it was shown by ISSR markers that a great amount of variation (49.26%) occurred between the two regions, with only 38.07%
and 12.66% between populations within regions and within a population respectively. Both the results of a UPGMA cluster, based
on Jaccard coefficients, and pairwise distance analysis agree with that of the AMOVA partition. This is the first report of
the partitioning of genetic variability within and among populations of O. granulata at the DNA level, which is in general agreement with a recent study on the same species in China using allozyme analysis.
Our results also indicated that the percentage of polymorphic bands (PPB) detected by ISSR is higher than that detected by
RAPD. It seems that ISSR is superior to RAPD in terms of the polymorphism detected and the amplification reproducibility.
Received: 29 March 2000 / Accepted: 15 May 2000 相似文献
39.
中国茶对变形链球菌的抑菌作用 总被引:2,自引:0,他引:2
对36只spraque-Dawley鼠分4组给予诱龋饲料(Diet2000,keys),并连续5天在口腔内接种变链菌6715菌株,分别给予我国主要产茶区的三种茶浸液:龙井绿茶(B组),四川涪陵红茶(C组),乌龙茶(D组),先用0.5g茶和50ml双蒸馏水加热煮沸过滤后浸泡10分钟以及对照组(A组)用双蒸馏水为饮料喂养实验鼠。实验60天后,杀鼠观察计算鼠磨牙面的菌落形成单位(CFU)和菌斑指数(plaquescore)均显著下降。实验结果,实验组和对照组菌斑指数下降值顺序如下:C组>D组>B组>A组,并与实验组含氟量有相关性。很多研究表明变链菌是较为肯定的致龋菌、茶中氟化物对变链菌生长、粘附都有抑制作用。本研究选用茶来源广泛、价廉、无毒安全等优点,为开拓新的防龋方法进行探索。 相似文献
40.
TLR4全长及其截断体重组腺病毒的制备和功能鉴定 总被引:2,自引:0,他引:2
制备脂多糖 (LPS)Toll样受体 4 (TLR4 )全长及其胞内段缺失的TLR4截断体 (ΔTLR4 )的绿色荧光蛋白重组腺病毒并鉴定其功能 .用PCR方法扩增TLR4及ΔTLR4基因片段 ,酶切后亚克隆至腺病毒穿梭质粒中 ,形成带有目的基因的穿梭载体pAdTrack TLR4和pAdTrack ΔTLR4 .用BJ5 1 83细菌同源重组法将目的基因重组于腺病毒骨架载体中 ;将重组腺病毒质粒用PacⅠ酶切线性化后 ,用脂质体法转染HEK 2 93细胞进行腺病毒的包装扩增 .将重组腺病毒感染CHO K1细胞 ,采用荧光毒酶报告基因方法检测其对LPS诱导NF κB激活的影响 .酶切及测序表明 ,TLR4全长及其截断体ΔTLR4的重组腺病毒载体构建正确 .荧光素酶报告基因检测结果表明 ,TLR4全长及其截断体的重组腺病毒感染细胞对LPS诱导的反应具有不同的影响 ,Ad ΔTLR4明显抑制了LPS引起的NF κB激活 (P <0 0 5 ) ,Ad TLR4则使LPS引起的NF κB活性增强 (P <0 0 5 ) .LPS对细胞的激活作用依赖于TLR4的结构完整性 相似文献