全文获取类型
收费全文 | 3912篇 |
免费 | 186篇 |
出版年
2021年 | 33篇 |
2020年 | 16篇 |
2019年 | 31篇 |
2018年 | 31篇 |
2017年 | 43篇 |
2016年 | 51篇 |
2015年 | 107篇 |
2014年 | 140篇 |
2013年 | 246篇 |
2012年 | 198篇 |
2011年 | 201篇 |
2010年 | 127篇 |
2009年 | 145篇 |
2008年 | 202篇 |
2007年 | 184篇 |
2006年 | 211篇 |
2005年 | 199篇 |
2004年 | 187篇 |
2003年 | 210篇 |
2002年 | 205篇 |
2001年 | 100篇 |
2000年 | 119篇 |
1999年 | 96篇 |
1998年 | 58篇 |
1997年 | 50篇 |
1996年 | 34篇 |
1995年 | 44篇 |
1994年 | 47篇 |
1993年 | 34篇 |
1992年 | 82篇 |
1991年 | 78篇 |
1990年 | 53篇 |
1989年 | 54篇 |
1988年 | 47篇 |
1987年 | 43篇 |
1986年 | 44篇 |
1985年 | 35篇 |
1984年 | 34篇 |
1983年 | 35篇 |
1982年 | 28篇 |
1981年 | 21篇 |
1980年 | 19篇 |
1979年 | 26篇 |
1978年 | 12篇 |
1977年 | 10篇 |
1976年 | 18篇 |
1975年 | 14篇 |
1973年 | 13篇 |
1970年 | 10篇 |
1969年 | 12篇 |
排序方式: 共有4098条查询结果,搜索用时 37 毫秒
1.
Timothy Truong Zachary A. Karlinski Christopher O’Hara Maleen Cabe Hongkyun Kim Joanna C. Bakowska 《PloS one》2015,10(6)
Troyer syndrome is caused by a mutation in the SPG20 gene, which results in complete loss of expression of the protein spartin. We generated a genetic model of Troyer syndrome in worms to explore the locomotor consequences of a null mutation of the Caenorhabditis elegans SPG20 orthologue, F57B10.9, also known as spg-20. Spg-20 mutants showed decreased length, crawling speed, and thrashing frequency, and had a shorter lifespan than wild-type animals. These results suggest an age-dependent decline in motor function in mutant animals. The drug paraquat was used to induce oxidative stress for 4 days in the animals. We measured survival rate and examined locomotion by measuring crawling speed and thrashing frequency. After 4 days of paraquat exposure, 77% of wild-type animals survived, but only 38% of spg-20 mutant animals survived. Conversely, animals overexpressing spg-20 had a survival rate of 95%. We also tested lifespan after a 1 hour exposure to sodium azide. After a 24 hour recovery period, 87% of wild type animals survived, 57% of spg-20 mutant animals survived, and 82% of animals overexpressing spg-20 survived. In the behavioral assays, spg-20 mutant animals showed a significant decrease in both crawling speed and thrashing frequency compared with wild-type animals. Importantly, the locomotor phenotype for both crawling and thrashing was rescued in animals overexpressing spg-20. The animals overexpressing spg-20 had crawling speeds and thrashing frequencies similar to those of wild-type animals. These data suggest that the protein F57B10.9/SPG-20 might have a protective role against oxidative stress. 相似文献
2.
Shota Yamana Amina Tokiyama Kiyohito Mizutani Ken-ichi Hirata Yoshimi Takai Yoshiyuki Rikitake 《PloS one》2015,10(4)
Contact inhibition of cell movement and proliferation is critical for proper organogenesis and tissue remodeling. We show here a novel regulatory mechanism for this contact inhibition using cultured vascular endothelial cells. When the cells were confluently cultured, Necl-4 was up-regulated and localized at cell–cell contact sites where it cis-interacted with the vascular endothelial growth factor (VEGF) receptor. This interaction inhibited the tyrosine-phosphorylation of the VEGF receptor through protein-tyrosine phosphatase, non-receptor type 13 (PTPN13), eventually reducing cell movement and proliferation. When the cells were sparsely cultured, Necl-4 was down-regulated but accumulated at leading edges where it inhibited the activation of Rho-associated protein kinase through PTPN13, eventually facilitating the VEGF-induced activation of Rac1 and enhancing cell movement. Necl-4 further facilitated the activation of extracellular signal-regulated kinase 1/2, eventually enhancing cell proliferation. Thus, Necl-4 serves as a novel regulator for contact inhibition of cell movement and proliferation cooperatively with the VEGF receptor and PTPN13. 相似文献
3.
4.
Nathan D. Mathewson Orr Ashenberg Itay Tirosh Simon Gritsch Elizabeth M. Perez Sascha Marx Livnat Jerby-Arnon Rony Chanoch-Myers Toshiro Hara Alyssa R. Richman Yoshinaga Ito Jason Pyrdol Mirco Friedrich Kathrin Schumann Michael J. Poitras Prafulla C. Gokhale L. Nicolas Gonzalez Castro Marni E. Shore Kai W. Wucherpfennig 《Cell》2021,184(5):1281-1298.e26
5.
Sumiko Hara Chisato Kaneko Hiroatsu Matsumoto Takeshi Nishino Tadao Takeuchi Takeo Mori 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):571-582
Abstract Novel β-D-ribofuranosides having a 5-substituted imidazo [4,5-d] [1,3]thiazine ring, including the S6-congener 3 of oxanosine 2, were synthesized for screening their anticancer and antiviral activities. 相似文献
6.
In several vascular inflammatory reactions (i.e. immunity and thrombosis) inflammatory mediators lead to the activation of vascular endothelial cells (EC). To date, a number
of functional molecules induced on the surface of activated-EC have been identified. We report here that Globotetraosylceramide
(Gb4), a glycosphingolipid expressed in EC, is a novel inducible molecule on EC activated by TNF-α. The cell surface expression
of Gb4 is increased in a time-dependent manner under TNF-α stimulation, which shows distinct expression kinetics of major
proteins induced by TNF-α on EC. MALDI-TOF-MS analysis revealed that the enhanced Gb4 predominantly contains C24:0 fatty acid
in the ceramide moiety. Isolated caveolae/lipid raft-enriched detergent insoluble membrane domains in activated-EC predominantly
contain this molecular species of Gb4. Gb4 containing C16:0 fatty acid in the ceramide moiety, which is known to constitute
the major species of Gb4 in plasma, is also found as a major molecular species in EC. These observations indicate that Gb4,
especially with very long fatty acid, is enhanced in EC during its inflammatory reaction, and suggest the potential utility
of Gb4 as a biomarker for monitoring inflammation status of EC involving its related diseases. 相似文献
7.
Comparative study on amino acid sequences of Kunitz-type soybean trypsin inhibitors, Tia, Tib, and Tic 总被引:10,自引:0,他引:10
S H Kim S Hara S Hase T Ikenaka H Toda K Kitamura N Kaizuma 《Journal of biochemistry》1985,98(2):435-448
The amino acid sequences of three variants of the Kunitz-type trypsin inhibitors, Tia, Tib, and Tic, obtained from some cultivars of soybean were determined by conventional methods. All three inhibitors consisted of 181 amino acid residues. The differences in the amino acid sequences are as follows: Tia E12 G55 Y62 H71 S74 M114 L120 P137 L176; Tib S F N R V I T V; Tic E. The amino acid sequences of Pro(60)-Ser(61) and Asp(154)-Asp(155)-Gly(156)-His(157) of Tia reported previously (Koide & Ikenaka (1973) Eur. J. Biochem. 32, 417-431) were amended to Ser(60)-Pro(61) and His(154)-Asp-Asp-Gly(157), respectively. 相似文献
8.
Taiichiro Okajima Toshiharu Motomatsu Ken-ichi Kato Hiroshi Ibayashi 《Life sciences》1980,26(9):699-705
Intraventicular injection of beta-endorphin (beta LPH61?91) in urethane anesthetized male rats led to a dose dependent increase of plasma prolactin levels. Intravenous injection of apomorphine completely abolished the stimulatory effect of beta-endorphin. Animals treated with 6-hydroxydopamine (6-OHDA) and 6-OHDA plus desmethylimipramine showed inhibition of beta-endorphin induced prolactin release. These results suggest that beta-endorphin presynaptically inhibits the activity of dopaminergic neurones, leading to the stimulation of plasma prolactin levels. 相似文献
9.
Steven I. Higgins Robert B. O’Hara Olga Bykova Michael D. Cramer Isabelle Chuine Eva‐Maria Gerstner Thomas Hickler Xavier Morin Michael R. Kearney Guy F. Midgley Simon Scheiter 《Journal of Biogeography》2012,39(12):2132-2145
Aim To develop a physiologically based model of the plant niche for use in species distribution modelling. Location Europe. Methods We link the Thornley transport resistance (TTR) model with functions which describe how the TTR’s model parameters are influenced by abiotic environmental factors. The TTR model considers how carbon and nutrient uptake, and the allocation of these assimilates, influence growth. We use indirect statistical methods to estimate the model parameters from a high resolution data set on tree distribution for 22 European tree species. Results We infer, from distribution data and abiotic forcing data, the physiological niche dimensions of 22 European tree species. We found that the model fits were reasonable (AUC: 0.79–0.964). The projected distributions were characterized by a false positive rate of 0.19 and a false negative rate 0.12. The fitted models are used to generate projections of the environmental factors that limit the range boundaries of the study species. Main conclusions We show that physiological models can be used to derive physiological niche dimensions from species distribution data. Future work should focus on including prior information on physiological rates into the parameter estimation process. Application of the TTR model to species distribution modelling suggests new avenues for establishing explicit links between distribution and physiology, and for generating hypotheses about how ecophysiological processes influence the distribution of plants. 相似文献
10.