全文获取类型
收费全文 | 6450篇 |
免费 | 641篇 |
国内免费 | 244篇 |
出版年
2024年 | 9篇 |
2023年 | 90篇 |
2022年 | 83篇 |
2021年 | 222篇 |
2020年 | 344篇 |
2019年 | 419篇 |
2018年 | 292篇 |
2017年 | 222篇 |
2016年 | 237篇 |
2015年 | 263篇 |
2014年 | 314篇 |
2013年 | 505篇 |
2012年 | 279篇 |
2011年 | 274篇 |
2010年 | 246篇 |
2009年 | 324篇 |
2008年 | 345篇 |
2007年 | 305篇 |
2006年 | 282篇 |
2005年 | 234篇 |
2004年 | 227篇 |
2003年 | 172篇 |
2002年 | 173篇 |
2001年 | 128篇 |
2000年 | 120篇 |
1999年 | 143篇 |
1998年 | 111篇 |
1997年 | 106篇 |
1996年 | 67篇 |
1995年 | 104篇 |
1994年 | 74篇 |
1993年 | 62篇 |
1992年 | 69篇 |
1991年 | 67篇 |
1990年 | 51篇 |
1989年 | 40篇 |
1988年 | 38篇 |
1987年 | 45篇 |
1986年 | 36篇 |
1985年 | 41篇 |
1984年 | 27篇 |
1983年 | 15篇 |
1982年 | 28篇 |
1981年 | 22篇 |
1980年 | 17篇 |
1979年 | 14篇 |
1978年 | 6篇 |
1977年 | 11篇 |
1976年 | 9篇 |
1974年 | 7篇 |
排序方式: 共有7335条查询结果,搜索用时 15 毫秒
1.
The laminated structure of the optic tectum is formed by radial and tangential cell migration during development. Studies of developing chick optic tectum have revealed two streams of tangential cell migration in the middle and superficial layers, which have distinctive origins, migratory paths, modes of migration, and destinations. We will review the process of the two types of tangential migrations, in order to elucidate their roles in the formation of the optic tectum layers. 相似文献
2.
Maria Weinert Tharakeswari Selvakumar Travis S. Tierney Kambiz N. Alavian 《Journal of visualized experiments : JoVE》2015,(96)
Degeneration of mesencephalic dopaminergic (mesDA) neurons is the pathological hallmark of Parkinson’s diseae. Study of the biological processes involved in physiological functions and vulnerability and death of these neurons is imparative to understanding the underlying causes and unraveling the cure for this common neurodegenerative disorder. Primary cultures of mesDA neurons provide a tool for investigation of the molecular, biochemical and electrophysiological properties, in order to understand the development, long-term survival and degeneration of these neurons during the course of disease. Here we present a detailed method for the isolation, culturing and maintenance of midbrain dopaminergic neurons from E12.5 mouse (or E14.5 rat) embryos. Optimized cell culture conditions in this protocol result in presence of axonal and dendritic projections, synaptic connections and other neuronal morphological properties, which make the cultures suitable for study of the physiological, cell biological and molecular characteristics of this neuronal population. 相似文献
3.
4.
5.
Hyun-Jin Kang Tuong Vy Thi Le Kyungmin Kim Jeonghwan Hur Kyeong Kyu Kim Hyun-Ju Park 《Journal of molecular biology》2014
Both G-quadruplex and Z-DNA can be formed in G-rich and repetitive sequences on genome, and their formation and biological functions are controlled by specific proteins. Z-DNA binding proteins, such as human ADAR1, have a highly conserved Z-DNA binding domain having selective affinity to Z-DNA. Here, our study identifies the Z-DNA binding domain of human ADAR1 (hZαADAR1) as a novel G-quadruplex binding protein that recognizes c-myc promoter G-quadruplex formed in NHEIII1 region and represses the gene expression. An electrophoretic migration shift assay shows the binding of hZαADAR1 to the intramolecular c-myc promoter G-quadruplex-forming DNA oligomer. To corroborate the binding of hZαADAR1 to the G-quadruplex, we conducted CD and NMR chemical shift perturbation analyses. CD results indicate that hZαADAR1 stabilizes the parallel-stranded conformation of the c-myc G-quadruplex. The NMR chemical shift perturbation data reveal that the G-quadruplex binding region in hZαADAR1 was almost identical with the Z-DNA binding region. Finally, promoter assay and Western blot analysis show that hZαADAR1 suppresses the c-myc expression promoted by NHEIII1 region containing the G-quadruplex-forming sequence. This finding suggests a novel function of Z-DNA binding protein as a regulator of G-quadruplex-mediated gene expression. 相似文献
6.
Sylvia Hofmann Sabine Kraus Tsering Dorge Michael Nothnagel Georg Miehe 《Journal of Biogeography》2014,41(11):2162-2172
7.
Secondary metastases are the leading cause of mortality in patients with breast cancer. Cytochrome P450 (CYP) 2J2 (CYP2J2) is upregulated in many human tumors and generates epoxyeicosanoids from arachidonic acid that promote tumorigenesis and metastasis, but at present there is little information on the genes that mediate these actions. In this study MDA-MB-468 breast cancer cells were stably transfected with CYP2J2 (MDA-2J2 cells) and Affymetrix microarray profiling was undertaken. We identified 182 genes that were differentially expressed in MDA-2J2 cells relative to control (MDA-CTL) cells (log[fold of control] ≥2). From gene ontology pathway analysis bone morphogenetic protein (BMP) receptor 1B (BMPR1B) emerged as an important upregulated gene in MDA-2J2 cells. Addition of the BMPR1B ligand BMP2 stimulated the migration of MDA-2J2 cells, but not MDA-CTL cells, from 3D-matrigel droplets. Migration of MDA-2J2 cells was prevented by the BMPR antagonist dorsomorphin. These findings indicate that over-expression of CYP2J2 in MDA-MB-468-derived breast cancer cells activates BMPR1B expression that may contribute to increased migration. Targeting BMPR1B may be a novel approach to inhibit the metastatic activity of breast cancers that contain high levels of CYP2J2. 相似文献
8.
Dong-Hui Xu Guo-Nan Chi Cong-Hai Zhao Dong-Yuan Li 《Journal of cellular biochemistry》2019,120(5):7516-7526
Glioma is a common primary brain tumor with high mortality rate and poor prognosis. Long noncoding RNA maternally expressed gene 3 (MEG3) is a tumor suppressor in diverse cancer types. However, the role of MEG3 in glioma remains unclear. We aimed to explore the effects of MEG3 on U251 cells as well as the underlying mechanisms. U251 cells were stably transfected with different recombined plasmids to overexpress or silence MEG3. Effects of aberrantly expressed MEG3 on cell viability, migration, apoptosis, expressions of apoptosis-associated and autophagy-associated proteins, and phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathway were all evaluated. Then, messenger RNA (mRNA) and protein expression of Sirt7 in cells abnormally expressing MEG3 were estimated. In addition, effects of abnormally expressed MEG3 and Sirt7 on U251 cells were determined to reveal the underlying mechanism of MEG3-associated modulation. Cell viability and migration were significantly reduced by MEG3 overexpression whereas cell apoptosis as well as Bax and cleaved caspase-3/-9 proteins were obviously induced. Beclin-1 and LC3-II/LC3-I were upregulated and p62 was downregulated in MEG3 overexpressed cells. In addition, the autophagy pharmacological inhibitor (3-methyladenine, 3-MA) affected the effect of MEG3 overexpression on cell proliferation. Furthermore, the phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathway were all reduced by MEG3 overexpression. Sirt7 was positively regulated by MEG3 expression, and effects of MEG3 overexpression on U251 cells were ameliorated by Sirt7 silence. MEG3 suppressed cell proliferation and migration but promoted autophagy in U251 cells through positively regulating Sirt7, involving in the inhibition of the PI3K/AKT/mTOR pathway. 相似文献
9.
《Cell calcium》2018
Store-operated calcium entry (SOCE) is the flow of calcium ions (Ca2+) into cells in response to the depletion of intracellular Ca2+ stores that reside predominantly in the endoplasmic reticulum (ER). The role of SOCE has been relatively well understood for non-excitable cells. It is mediated mostly by the ER Ca2+ sensor STIM1 and plasma membrane Ca2+ channel Orai1 and serves to sustain Ca2+ signaling and refill ER Ca2+ stores. In contrast, because of the complexity of Ca2+ influx mechanisms that are present in excitable cells, our knowledge about the function of neuronal SOCE (nSOCE) is still nascent. This review summarizes the available data on the molecular components of nSOCE and their relevance to neuronal signaling. We also present evidence of disturbances of nSOCE in neurodegenerative diseases (namely Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease) and traumatic brain injury. The emerging important role of nSOCE in neuronal physiology and pathology makes it a possible clinical target. 相似文献
10.
《Current biology : CB》2020,30(20):4085-4095.e6