全文获取类型
收费全文 | 8074篇 |
免费 | 596篇 |
国内免费 | 41篇 |
出版年
2024年 | 7篇 |
2023年 | 34篇 |
2022年 | 97篇 |
2021年 | 175篇 |
2020年 | 123篇 |
2019年 | 190篇 |
2018年 | 246篇 |
2017年 | 201篇 |
2016年 | 326篇 |
2015年 | 482篇 |
2014年 | 552篇 |
2013年 | 597篇 |
2012年 | 740篇 |
2011年 | 691篇 |
2010年 | 498篇 |
2009年 | 417篇 |
2008年 | 527篇 |
2007年 | 486篇 |
2006年 | 369篇 |
2005年 | 362篇 |
2004年 | 311篇 |
2003年 | 273篇 |
2002年 | 275篇 |
2001年 | 102篇 |
2000年 | 126篇 |
1999年 | 105篇 |
1998年 | 48篇 |
1997年 | 46篇 |
1996年 | 31篇 |
1995年 | 29篇 |
1994年 | 20篇 |
1993年 | 21篇 |
1992年 | 21篇 |
1991年 | 30篇 |
1990年 | 22篇 |
1989年 | 19篇 |
1988年 | 11篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1983年 | 10篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1970年 | 3篇 |
1969年 | 4篇 |
1968年 | 3篇 |
排序方式: 共有8711条查询结果,搜索用时 265 毫秒
51.
Hyo Je Cho Kyungsun Kim Seo Yean Sohn Ha Yeon Cho Kyung Jin Kim Myung Hee Kim Dockyu Kim Eungbin Kim Beom Sik Kang 《The Journal of biological chemistry》2010,285(45):34643-34652
A meta-cleavage pathway for the aerobic degradation of aromatic hydrocarbons is catalyzed by extradiol dioxygenases via a two-step mechanism: catechol substrate binding and dioxygen incorporation. The binding of substrate triggers the release of water, thereby opening a coordination site for molecular oxygen. The crystal structures of AkbC, a type I extradiol dioxygenase, and the enzyme substrate (3-methylcatechol) complex revealed the substrate binding process of extradiol dioxygenase. AkbC is composed of an N-domain and an active C-domain, which contains iron coordinated by a 2-His-1-carboxylate facial triad motif. The C-domain includes a β-hairpin structure and a C-terminal tail. In substrate-bound AkbC, 3-methylcatechol interacts with the iron via a single hydroxyl group, which represents an intermediate stage in the substrate binding process. Structure-based mutagenesis revealed that the C-terminal tail and β-hairpin form part of the substrate binding pocket that is responsible for substrate specificity by blocking substrate entry. Once a substrate enters the active site, these structural elements also play a role in the correct positioning of the substrate. Based on the results presented here, a putative substrate binding mechanism is proposed. 相似文献
52.
Several studies have shown that repeated stressful experiences during childhood increases the likelihood of developing depression- and anxiety-related disorders in adulthood; however, the underlying mechanisms are not well understood. We subjected drd3-EGFP and drd3-null mice to daily, two hour restraint stress episodes over a five day period during preadolescence (postnatal day 35 to 39), followed by social isolation. When these mice reached adulthood (post-natal day > 90), we assessed locomotor behavior in a novel environment, and assessed depression-related behavior in the Porsolt Forced Swim test. We also measured the expression and function of dopamine D3 receptor in limbic brain areas such as hippocampus, nucleus accumbens and amygdala in control and stressed drd3-EGFP mice in adulthood. Adult male mice subjected to restraint stress during preadolescence exhibited both anxiety- and depression-related behaviors; however, adult female mice subjected to preadolescent restraint stress exhibited only depression-related behaviors. The development of preadolescent stress-derived psychiatric disorders was blocked by D3 receptor selective antagonist, SB 277011-A, and absent in D3 receptor null mice. Adult male mice that experienced stress during preadolescence exhibited a loss of D3 receptor expression and function in the amygdala but not in hippocampus or nucleus accumbens. In contrast, adult female mice that experienced preadolescent stress exhibited increased D3 receptor expression in the nucleus accumbens but not in amygdala or hippocampus. Our results suggest that the dopamine D3 receptor is centrally involved in the etiology of adult anxiety- and depression-related behaviors that arise from repeated stressful experiences during childhood. 相似文献
53.
Il Sang Yoon 《Analytical biochemistry》2010,407(2):205-210
Parkinson’s disease (PD) is a neurodegenerative disease featured by selective loss of substantia nigra neurons. Rotenone administration in animals induces neurodegeneration accompanied by α-synuclein-positive Lewy body-like inclusions, recapturing typical histopathological features of PD. In an effort to screen for small-molecule agents to reverse rotenone-induced cytotoxicity, we developed and validated a sensitive and robust assay with neuroblastoma SK-N-SH cells. This assay was amenable to a high-throughput screening format with Z′ factor of 0.56. Robotic screening of a bioactive compound library led to the identification of carnosic acid that can effectively protect cells from rotenone treatment. Using a high-content image-based assay and Western blot analysis, we demonstrated that carnosic acid protects cells from rotenone stress by significant induction of HSP70 expression. Therefore, the assay reported here can be used to identify novel cytoprotective agents for clinical therapeutics of PD. 相似文献
54.
Subdural cortical stimulation (SuCS) is a method used to inject electrical current through electrodes beneath the dura mater, and is known to be useful in treating brain disorders. However, precisely how SuCS must be applied to yield the most effective results has rarely been investigated. For this purpose, we developed a three-dimensional computational model that represents an anatomically realistic brain model including an upper chest. With this computational model, we investigated the influence of stimulation amplitudes, electrode configurations (single or paddle-array), and white matter conductivities (isotropy or anisotropy). Further, the effects of stimulation were compared with two other computational models, including an anatomically realistic brain-only model and the simplified extruded slab model representing the precentral gyrus area. The results of voltage stimulation suggested that there was a synergistic effect with the paddle-array due to the use of multiple electrodes; however, a single electrode was more efficient with current stimulation. The conventional model (simplified extruded slab) far overestimated the effects of stimulation with both voltage and current by comparison to our proposed realistic upper body model. However, the realistic upper body and full brain-only models demonstrated similar stimulation effects. In our investigation of the influence of anisotropic conductivity, model with a fixed ratio (1∶10) anisotropic conductivity yielded deeper penetration depths and larger extents of stimulation than others. However, isotropic and anisotropic models with fixed ratios (1∶2, 1∶5) yielded similar stimulation effects. Lastly, whether the reference electrode was located on the right or left chest had no substantial effects on stimulation. 相似文献
55.
Shi-Liang Zhou Xin-Hui Zou Zhi-Qin Zhou Jing Liu Chao Xu Jing Yu Qiang Wang Da-Ming Zhang Xiao-Quan Wang Song Ge Tao Sang Kai-Yu Pan De-Yuan Hong 《Proceedings. Biological sciences / The Royal Society》2014,281(1797)
The origin of cultivated tree peonies, known as the ‘king of flowers'' in China for more than 1000 years, has attracted considerable interest, but remained unsolved. Here, we conducted phylogenetic analyses of explicitly sampled traditional cultivars of tree peonies and all wild species from the shrubby section Moutan of the genus Paeonia based on sequences of 14 fast-evolved chloroplast regions and 25 presumably single-copy nuclear markers identified from RNA-seq data. The phylogeny of the wild species inferred from the nuclear markers was fully resolved and largely congruent with morphology and classification. The incongruence between the nuclear and chloroplast trees suggested that there had been gene flow between the wild species. The comparison of nuclear and chloroplast phylogenies including cultivars showed that the cultivated tree peonies originated from homoploid hybridization among five wild species. Since the origin, thousands of cultivated varieties have spread worldwide, whereas four parental species are currently endangered or on the verge of extinction. The documentation of extensive homoploid hybridization involved in tree peony domestication provides new insights into the mechanisms underlying the origins of garden ornamentals and the way of preserving natural genetic resources through domestication. 相似文献
56.
Jung Dong-Hyun Seo Dong-Ho Kim Ga-Young Nam Young-Do Song Eun-Ji Yoon Shawn Park Cheon-Seok 《Applied microbiology and biotechnology》2018,102(11):4927-4936
Applied Microbiology and Biotechnology - Resistant starch (RS) in the diet reaches the large intestine without degradation, where it is decomposed by the commensal microbiota. The fermentation of... 相似文献
57.
In this paper, three Korean species of the big‐head fly, genus Jassidophaga Aczél were treated: J. chiiensis (Ouchi), J. pala (Morakote) and J. villosa (Roser). Of these, J. pala is reported in Korea for the first time. A key to Korean species and photographs on external features are given. 相似文献
58.
Hae-ock Lee Hyerim Choe Kyungwoon Seo Hyunsook Lee Jinseon Lee Jhingook Kim 《Molecules and cells》2010,29(5):501-507
Fibroblast growth factor binding protein 1 (FGFBP1) is expressed in various tumors and may serve as a diagnostic marker and/or
a therapeutic target. Previous studies suggested FGFBP1 functions as an angiogenic switch molecule by regulating the activity
of FGF2, and it was later found to associate with a broad spectrum of FGFs. To study FGFBP1, we used zebrafish, in which the
function of extracellular matrix protein can be easily studied in intact tissues or organisms. When Fgfbp1 expression was
knocked down, morphants manifested massive cell death and structural abnormalities. Cell death was most prominent in the brain
and the neural tube, but not limited to those regions. These findings suggest that the primary function of Fgfbp1 may be to
sustain cellular survival throughout embryogenesis. For comparison, the expression of fgf2 was limited to the early stage of embryogenesis and fgf2 morphants showed more severe phenotype, with high morbidity before reaching 14-somites. Taken together, our work reveals
the physiologic function of Fgfbp1, and that its function could be exerted in a Fgf2-independent manner. 相似文献
59.
James D. Glover Lorna Taylor Adrian Sherman Caroline Zeiger-Poli Helen M. Sang Michael J. McGrew 《PloS one》2013,8(11)
In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC) lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development. 相似文献
60.
Yong-Bin Cho Sungguan Hong Kyung-Won Kang Ji-Hun Kang Sang-Myeong Lee Young-Jin Seo 《Journal of cellular and molecular medicine》2020,24(10):5463-5475
The influenza virus is one of the major public health threats. However, the development of efficient vaccines and therapeutic drugs to combat this virus is greatly limited by its frequent genetic mutations. Because of this, targeting the host factors required for influenza virus replication may be a more effective strategy for inhibiting a broader spectrum of variants. Here, we demonstrated that inhibition of a motor protein kinesin family member 18A (KIF18A) suppresses the replication of the influenza A virus (IAV). The expression of KIF18A in host cells was increased following IAV infection. Intriguingly, treatment with the selective and ATP-competitive mitotic kinesin KIF18A inhibitor BTB-1 substantially decreased the expression of viral RNAs and proteins, and the production of infectious viral particles, while overexpression of KIF18A enhanced the replication of IAV. Importantly, BTB-1 treatment attenuated the activation of AKT, p38 MAPK, SAPK and Ran-binding protein 3 (RanBP3), which led to the prevention of the nuclear export of viral ribonucleoprotein complexes. Notably, administration of BTB-1 greatly improved the viability of IAV-infected mice. Collectively, our results unveiled a beneficial role of KIF18A in IAV replication, and thus, KIF18A could be a potential therapeutic target for the control of IAV infection. 相似文献