全文获取类型
收费全文 | 21175篇 |
免费 | 954篇 |
国内免费 | 603篇 |
出版年
2023年 | 331篇 |
2022年 | 474篇 |
2021年 | 569篇 |
2020年 | 612篇 |
2019年 | 825篇 |
2018年 | 693篇 |
2017年 | 423篇 |
2016年 | 420篇 |
2015年 | 502篇 |
2014年 | 1093篇 |
2013年 | 1609篇 |
2012年 | 776篇 |
2011年 | 1107篇 |
2010年 | 745篇 |
2009年 | 860篇 |
2008年 | 931篇 |
2007年 | 955篇 |
2006年 | 806篇 |
2005年 | 726篇 |
2004年 | 650篇 |
2003年 | 535篇 |
2002年 | 433篇 |
2001年 | 325篇 |
2000年 | 253篇 |
1999年 | 273篇 |
1998年 | 285篇 |
1997年 | 236篇 |
1996年 | 238篇 |
1995年 | 191篇 |
1994年 | 177篇 |
1993年 | 161篇 |
1992年 | 162篇 |
1991年 | 144篇 |
1990年 | 142篇 |
1989年 | 124篇 |
1988年 | 118篇 |
1987年 | 125篇 |
1985年 | 242篇 |
1984年 | 422篇 |
1983年 | 331篇 |
1982年 | 397篇 |
1981年 | 312篇 |
1980年 | 319篇 |
1979年 | 325篇 |
1978年 | 238篇 |
1977年 | 217篇 |
1976年 | 192篇 |
1975年 | 164篇 |
1974年 | 165篇 |
1973年 | 161篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
31.
32.
Marjorie Jones Roy W. Keenan 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,678(3):403-407
A procedure was developed for the detection of 2′,3′-cyclic nucleotide 3′-phosphohydrolase in myelin. This assay was sufficiently sensitive to detect the low levels of 2′,3′-cyclic nucleotide 3′-phosphohydrolase in human erythrocytes. The 2′,3′-cyclic nucleotide 3′-phosphohydrolase of human erythrocytes was determined to be exclusively associated with the inner (cytosolic) side of the membrane. Leaky ghostsand resealed ghosts were assayed for 2′,3′-cyclic nucleotide 3′-phosphohydrolase, (Ca2+/Mg2+-ATPase, and acetylcholinesterase activity, and the 2′,3′-cyclic nucleotide 3′-phosphohydrolase profile is the same as that of the (Ca2+/Mg2+)-ATPase, an established inner membrane maker. 相似文献
33.
Johnathan L Meaders Erica F Geers Belen Fernandez‐Garcia Marvin E Tanenbaum 《The EMBO journal》2012,31(21):4179-4190
The microtubule motor protein kinesin‐5 (Eg5) provides an outward force on centrosomes, which drives bipolar spindle assembly. Acute inhibition of Eg5 blocks centrosome separation and causes mitotic arrest in human cells, making Eg5 an attractive target for anti‐cancer therapy. Using in vitro directed evolution, we show that human cells treated with Eg5 inhibitors can rapidly acquire the ability to divide in the complete absence of Eg5 activity. We have used these Eg5‐independent cells to study alternative mechanisms of centrosome separation. We uncovered a pathway involving nuclear envelope (NE)‐associated dynein that drives centrosome separation in prophase. This NE‐dynein pathway is essential for bipolar spindle assembly in the absence of Eg5, but also functions in the presence of full Eg5 activity, where it pulls individual centrosomes along the NE and acts in concert with Eg5‐dependent outward pushing forces to coordinate prophase centrosome separation. Together, these results reveal how the forces are produced to drive prophase centrosome separation and identify a novel mechanism of resistance to kinesin‐5 inhibitors. 相似文献
34.
Background
Eosinophilia plays the major role in the pathogenesis of asthma and correlates with the up‐regulation of eotaxin, which, together with interleukin (IL)‐5, is important for differentiation, chemo‐attraction, degranulation, and survival of eosinophils in local tissue. In a previous study, we found that administration of lentivirus‐delivered short hairpin RNA (shRNA) to suppress the expression of IL‐5 inhibited airway inflammation. The present study aimed to investigate the role of eotaxin shRNA and the synergistic effect of eotaxin and IL‐5 shRNAs on airway inflammation in an ovalbumin (OVA)‐induced murine model of asthma.Methods
Lentivirus‐delivered shRNAs were used to suppress the expression of eotaxin and/or IL‐5 in local tissue in an OVA‐induced murine asthma model.Results
Intra‐tracheal administration of lentivirus containing eotaxin shRNA expressing cassette (eoSEC3.3) efficiently moderated the characteristics of asthma, including airway hyper‐responsiveness, cellular infiltration of lung tissues, and eotaxin and IL‐5 levels in bronchio‐alveolar lavage fluid. Administration of lentiviruses expressing IL‐5 or eotaxin shRNAs (IL5SEC4 + eoSEC3.3) also moderated the symptoms of asthma in a mouse model.Conclusions
Local delivery of lentiviruses expressing IL‐5 and eotaxin shRNAs provides a potential tool in moderating airway inflammation and also has the potential for developing clinical therapy based on the application of shRNAs of chemokines and cytokines involved in T helper 2 cell inflammation and eosinophilia. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献35.
《Bioorganic & medicinal chemistry letters》2020,30(11):127150
People with reduced esterase D (ESD) activity are susceptible to many diseases. However, how to activate ESD is still unknown. To address the question, we identified that 4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4, 5-dihydro-1H-pyrazol-3-yl) phenol (FPD5) could be a good candidate activator for ESD activity. We found that FPD5 could increase ESD activity in a dose-dependent way. FPD5 bound directly to ESD at Lys180 rather than its ubiquitination site Lys213. Site-directed mutagenesis at the binding site or the ubiquitination site inhibited FPD5 action. FPD5 increased the level of ESD mono-ubiquitination and mutESD K213A completely inhibited this action. Our findings highlighted the activation mechanism of ESD via promoting the mono-ubiquitination of ESD. 相似文献
36.
《Bioorganic & medicinal chemistry letters》2020,30(16):127289
The present research project details synthesis of new hybrid methanofullerenes based on acetylene and triazole esters of malonic acid containing 5Z,9Z-dienoic acids and fullerene C60 under Bingel-Hirsch conditions, including study of the cytotoxic activity with respect to Jurkat, K562, U937 and HL60 tumor cell lines. Hybrid methanofullerenes containing acetylenic fragments, unlike triazole substituents, were found to exhibit higher cytotoxicity, but are characterized by lower selectivity of action in relation to healthy cells. 相似文献
37.
《Bioorganic & medicinal chemistry letters》2014,24(10):2329-2333
The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly inhibited pancreatic lipase, which plays a key role in fat absorption. Optimization of extraction conditions with minimum pancreatic lipase activity and maximum yield was determined using response surface methodology with three-level-three-factor Box–Behnken design (BBD). Regression analysis showed a good fit of the experimental data and the optimal condition was obtained as ethanol concentration, 74.5%; temperature 61.9 °C and extraction time, 13.5 h. The pancreatic lipase activity and extraction yield under optimal conditions were found to be 65.5% and 54.0%, respectively, which were well matched with the predicted value of 65.8% and 47.1%. Further fractionation of C. tricuspidata extract resulted in the isolation of compound 1, which was identified as 5,7,4′-trihydroxy-6,8-diprenylisoflavone. It inhibited pancreatic lipase activity with IC50 value of 65.0 μM. HPLC analysis suggested positive correlation between pancreatic lipase inhibition and 5,7,4′-trihydroxy-6,8-diprenylisoflavone of C. tricuspidata fruits. 相似文献
38.
Mr Gaston H. M. Vondenhoff Arthur Van Aerschot 《Nucleosides, nucleotides & nucleic acids》2013,32(7-8):465-474
The natural compound Microcin C (McC) is a Trojan horse inhibitor of aspartyl tRNA synthetases endowed with strong antibacterial properties, in which a heptapeptide moiety is responsible for active transport of the inhibitory metabolite part into the bacterial cell. The intracellularly formed aspartyl AMP analogue carries a chemically more stable phosphoramidate linkage, in comparison to the labile aspartyl-adenylate, and in addition is esterified with a 3-aminopropyl moiety. Therefore, this compound can target aspartyl-tRNA synthetase. The biochemical production and secretion of McC, and the possibilities to develop new classes of antibiotics using the McC Trojan horse concept in combination with sulfamoylated adenosine analogues will be discussed briefly. 相似文献
39.
40.