全文获取类型
收费全文 | 7721篇 |
免费 | 691篇 |
国内免费 | 1092篇 |
出版年
2024年 | 29篇 |
2023年 | 112篇 |
2022年 | 299篇 |
2021年 | 433篇 |
2020年 | 340篇 |
2019年 | 408篇 |
2018年 | 381篇 |
2017年 | 287篇 |
2016年 | 337篇 |
2015年 | 465篇 |
2014年 | 604篇 |
2013年 | 662篇 |
2012年 | 743篇 |
2011年 | 619篇 |
2010年 | 438篇 |
2009年 | 410篇 |
2008年 | 419篇 |
2007年 | 381篇 |
2006年 | 335篇 |
2005年 | 297篇 |
2004年 | 269篇 |
2003年 | 260篇 |
2002年 | 199篇 |
2001年 | 161篇 |
2000年 | 113篇 |
1999年 | 96篇 |
1998年 | 74篇 |
1997年 | 48篇 |
1996年 | 55篇 |
1995年 | 42篇 |
1994年 | 39篇 |
1993年 | 31篇 |
1992年 | 21篇 |
1991年 | 21篇 |
1990年 | 15篇 |
1989年 | 14篇 |
1988年 | 10篇 |
1987年 | 13篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1950年 | 1篇 |
排序方式: 共有9504条查询结果,搜索用时 15 毫秒
271.
272.
273.
274.
Jian Liang Jun Xie Jing Gao Chao-Qun Xu Yi Yan Gan-Chu Jia Liang Xiang Li-Ping Xie Rong-Qing Zhang 《Marine biotechnology (New York, N.Y.)》2016,18(6):645-658
Mantle can secret matrix proteins playing key roles in regulating the process of shell formation. The genes encoding lysine-rich matrix proteins (KRMPs) are one of the most highly expressed matrix genes in pearl oysters. However, the expression pattern of KRMPs is limited and the functions of them still remain unknown. In this study, we isolated and identified six new members of lysine-rich matrix proteins, rich in lysine, glycine and tyrosine, and all of them are basic matrix proteins. Combined with four members of the KRMPs previously reported, all these proteins can be divided into three subclasses according to the results of phylogenetic analyses: KRMP1–3 belong to subclass KPI, KRMP4–5 belong to KPII, and KRMP6–10 belong to KPIII. Three subcategories of lysine-rich matrix proteins are highly expressed in the D-phase, the larvae and adult mantle. Lysine-rich matrix proteins are involved in the shell repairing process and associated with the formation of the shell and pearl. What’s more, they can cause abnormal shell growth after RNA interference. In detail, KPI subgroup was critical for the beginning formation of the prismatic layer; both KPII and KPIII subgroups participated in the formation of prismatic layer and nacreous layer. Compared with different temperatures and salinity stimulation treatments, the influence of changes in pH on KRMPs gene expression was the greatest. Recombinant KRMP7 significantly inhibited CaCO3 precipitation, changed the morphology of calcite, and inhibited the growth of aragonite in vitro. Our results are beneficial to understand the functions of the KRMP genes during shell formation. 相似文献
275.
Two amino acids near the N‐terminus of Cucumber mosaic virus 2b play critical roles in the suppression of RNA silencing and viral infectivity 下载免费PDF全文
Kai Dong Ying Wang Zhen Zhang Long‐Xiang Chai Xin Tong Jin Xu Dawei Li Xian‐Bing Wang 《Molecular Plant Pathology》2016,17(2):173-183
Cucumber mosaic virus (CMV) 2b suppresses RNA silencing primarily through the binding of double‐stranded RNA (dsRNA) of varying sizes. However, the biologically active form of 2b remains elusive. Here, we demonstrate that the single and double alanine substitution mutants in the N‐terminal 15th leucine and 18th methionine of CMV 2b exhibit drastically attenuated virulence in wild‐type plants, but are efficiently rescued in mutant plants defective in RNA‐dependent RNA polymerase 6 (RDR6) and Dicer‐like 4 (DCL4). Moreover, the transgenic plants of 2b, but not 2blm (L15A/M18A), rescue the high infectivity of CMV‐Δ2b through the suppression of antiviral silencing. L15A, M18A or both weaken 2b suppressor activity on local and systemic transgene silencing. In contrast with the high affinity of 2b to short and long dsRNAs, 2blm is significantly compromised in 21‐bp duplex small interfering RNA (siRNA) binding ability, but maintains a strong affinity for long dsRNAs. In cross‐linking assays, 2b can form dimers, tetramers and oligomers after treatment with glutaraldehyde, whereas 2blm only forms dimers, rather than tetramers and oligomers, in vitro. Together, these findings suggest that L15 and M18 of CMV 2b are required for high affinity to ds‐siRNAs and oligomerization activity, which are essential for the suppression activity of 2b on antiviral silencing. 相似文献
276.
Xiaojuan Han Haoran Tai Xiaobo Wang Zhe Wang Jiao Zhou Xiawei Wei Yi Ding Hui Gong Chunfen Mo Jie Zhang Jianqiong Qin Yuanji Ma Ning Huang Rong Xiang Hengyi Xiao 《Aging cell》2016,15(3):416-427
AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress‐induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide‐induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP‐RFP‐LC3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD+ levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD+ synthesis. In addition, the mechanistic relationship of autophagic flux and NAD+ synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress‐induced senescence by improving autophagic flux and NAD+ homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD+ homeostasis, and it is also valuable in the development of innovative strategies to combat aging. 相似文献
277.
Yi-ning Wen Zhi-feng Zhang Ning-ning Liu Yu-hong Xiang Zhuo-yong Zhang Graciela Andrei 《Nucleosides, nucleotides & nucleic acids》2016,35(3):147-160
A series of novel trisubstituted 1,2,3-triazole purine nucleosides were efficiently synthesized via Huisgen 1,3-dipolar cycloaddition in good yields. Bioactivity against cytomegalovirus (CMV) and varicella-zoster virus (VZV) in human embryonic lung cell cultures was evaluated and all compounds show low antiviral activity. 相似文献
278.
In order to regulate the skin permeation rate (flux) of escitalopram (ESP), ion-pair strategy was used in our work. Five organic acids with different physicochemical properties, benzoic acid (BA), ibuprofen (IB), salicylic acid (SA), benzenesulfonic acid (BSA), and p-aminobenzoic acid (PABA), were employed as counter-ions to regulate the permeation rate of ESP across the rabbit abdominal skin in vitro. The interaction between ESP and organic acids was characterized by FTIR and 13C NMR spectroscopy. Results showed that all organic acids investigated in this study performed a controlling effect on ESP flux. To further analyze the factors concerned with the permeation capability of ESP-acid complex, a multiple linear regression model was used. It is concluded that the steady-state flux (J) of ESP-acid complexes had a positive correlation with log K o/w (the n-octanol/water partition coefficient of ion-pair complex) and pK a (the acidity of organic acid counter-ion), but a negative correlation with MW (the molecular weight of ion-pair complex). The logK o/w of ion-pair complex is the primary one in all the factors that influence the skin permeation rate of ESP. The results demonstrated that organic acid with appropriate physicochemical properties can be considered as suitable candidate for the transdermal drug delivery of escitalopram. 相似文献
279.
280.
Mechanism and rate constants of the Cdc42 GTPase binding with intrinsically disordered effectors 下载免费PDF全文
Intrinsically disordered proteins (IDPs) are often involved in signaling and regulatory functions, through binding to cellular targets. Many IDPs undergo disorder‐to‐order transitions upon binding. Both the binding mechanisms and the magnitudes of the binding rate constants can have functional importance. Previously we have found that the coupled binding and folding of any IDP generally follows a sequential mechanism that we term dock‐and‐coalesce, whereby one segment of the IDP first docks to its subsite on the target surface and the remaining segments subsequently coalesce around their respective subsites. Here we applied our TransComp method within the framework of the dock‐and‐coalesce mechanism to dissect the binding kinetics of two Rho‐family GTPases, Cdc42 and TC10, with two intrinsically disordered effectors, WASP and Pak1. TransComp calculations identified the basic regions preceding the GTPase binding domains (GBDs) of the effectors as the docking segment. For Cdc42 binding with both WASP and Pak1, the calculated docking rate constants are close to the observed overall binding rate constants, suggesting that basic‐region docking is the rate‐limiting step and subsequent conformational coalescence of the GBDs on the Cdc42 surface is fast. The possibility that conformational coalescence of the WASP GBD on the TC10 surface is slow warrants further experimental investigation. The account for the differences in binding rate constants among the three GTPase‐effector systems and mutational effects therein yields deep physical and mechanistic insight into the binding processes. Our approach may guide the selection of mutations that lead to redesigned binding pathways. Proteins 2016; 84:674–685. © 2016 Wiley Periodicals, Inc. 相似文献