全文获取类型
收费全文 | 10059篇 |
免费 | 737篇 |
国内免费 | 4篇 |
出版年
2024年 | 9篇 |
2023年 | 33篇 |
2022年 | 102篇 |
2021年 | 195篇 |
2020年 | 140篇 |
2019年 | 203篇 |
2018年 | 271篇 |
2017年 | 211篇 |
2016年 | 381篇 |
2015年 | 582篇 |
2014年 | 677篇 |
2013年 | 726篇 |
2012年 | 992篇 |
2011年 | 866篇 |
2010年 | 589篇 |
2009年 | 492篇 |
2008年 | 673篇 |
2007年 | 597篇 |
2006年 | 567篇 |
2005年 | 471篇 |
2004年 | 448篇 |
2003年 | 389篇 |
2002年 | 314篇 |
2001年 | 160篇 |
2000年 | 144篇 |
1999年 | 141篇 |
1998年 | 79篇 |
1997年 | 43篇 |
1996年 | 32篇 |
1995年 | 31篇 |
1994年 | 28篇 |
1993年 | 21篇 |
1992年 | 29篇 |
1991年 | 27篇 |
1990年 | 17篇 |
1989年 | 12篇 |
1988年 | 11篇 |
1987年 | 7篇 |
1986年 | 11篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1974年 | 8篇 |
1969年 | 4篇 |
1967年 | 5篇 |
1966年 | 5篇 |
1965年 | 3篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
Rouhana L Wang L Buter N Kwak JE Schiltz CA Gonzalez T Kelley AE Landry CF Wickens M 《RNA (New York, N.Y.)》2005,11(7):1117-1130
Cytoplasmic polyadenylation is important in the control of mRNA stability and translation, and for early animal development and synaptic plasticity. Here, we focus on vertebrate poly(A) polymerases that are members of the recently described GLD2 family. We identify and characterize two closely related GLD2 proteins in Xenopus oocytes, and show that they possess PAP activity in vivo and in vitro and that they bind known polyadenylation factors and mRNAs known to receive poly(A) during development. We propose that at least two distinct polyadenylation complexes exist in Xenopus oocytes, one of which contains GLD2; the other, maskin and Pumilio. GLD2 protein interacts with the polyadenylation factor, CPEB, in a conserved manner. mRNAs that encode GLD2 in mammals are expressed in many tissues. In the brain, mouse, and human GLD2 mRNAs are abundant in anatomical regions necessary for long-term cognitive and emotional learning. In the hippocampus, mouse GLD2 mRNA colocalizes with CPEB1 and Pumilio1 mRNAs, both of which are likely involved in synaptic plasticity. We suggest that mammalian GLD2 poly(A) polymerases are important in synaptic translation, and in polyadenylation throughout the soma. 相似文献
992.
Kim HJ Shin SW Oh CJ Lee MH Yang CH Park JW 《Redox report : communications in free radical research》2005,10(6):287-293
Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Therefore, compounds that scavenge reactive oxygen species may regulate heat shock-induced cell death. Recently, it has been shown that the decomposition product of the spin-trapping agent alpha-phenyl-N-t-butylnitrone, N-t-butyl hydroxylamine (NtBHA), mimics alpha-phenyl-N-t-butylnitrone and is much more potent in delaying reactive oxygen species-associated senescence. We investigated the protective role of NtBHA against heat shock-induced apoptosis in U937 cells. Upon exposure to heat shock, there was a distinct difference between the untreated cells and the cells pre-treated with 0.1 mM NtBHA for 2 h in regard to apoptotic parameters, cellular redox status, and mitochondrial function. Upon exposure to heat shock, NtBHA pre-treated cells showed significant inhibition of apoptotic features such as activation of caspase-3, up-regulation of Bax, and down-regulation of Bcl-2 compared to untreated cells. This study indicates that NtBHA may play an important role in regulating the apoptosis induced by heat shock, presumably through scavenging of reactive oxygen species. 相似文献
993.
Synthesis and biological activity of 3,4-dihydroquinazolines for selective T-type Ca2+ channel blockers 总被引:1,自引:0,他引:1
We have synthesized 3,4-dihydroquinazoline derivatives for the potent and selective T-type Ca(2+) channel blockers and evaluated for their inhibitory activities against two subtypes T-type Ca(2+) channels and N-type Ca(2+) channels. Among them, 5b (KYS05044, IC(50)=0.56+/-0.10 microM) was identified as potent T-type Ca(2+) channel blocker with in vitro selectivity profile at meaningful level (T/N-type, SI=>100). 相似文献
994.
The molecular basis of odor coding in the Drosophila larva 总被引:2,自引:0,他引:2
We have analyzed the molecular basis of odor coding in the Drosophila larva. A subset of Or genes is found to be expressed in larval olfactory receptor neurons (ORNs). Using an in vivo expression system and electrophysiology, we demonstrate that these genes encode functional odor receptors and determine their response spectra with 27 odors. The receptors vary in their breadth of tuning, exhibit both excitation and inhibition, and show different onset and termination kinetics. An individual receptor appears to transmit signals via a single ORN to a single glomerulus in the larval antennal lobe. We provide a spatial map of odor information in the larval brain and find that ORNs with related functional specificity map to related spatial positions. The results show how one family of receptors underlies odor coding in two markedly different olfactory systems; they also provide a molecular mechanism to explain longstanding observations of larval odor discrimination. 相似文献
995.
Sphingosylphosphorylcholine (SPC) is a bioactive lipid molecule involved in numerous biological processes. Treatment of MS1 pancreatic islet endothelial cells with SPC increased phospholipase D (PLD) activity in a time- and dose-dependent manner. In addition, treatment of the MS1 cells with 10 microM SPC induced stimulation of phospholipase C (PLC) activity and transient elevation of intracellular Ca2+. The SPC-induced PLD activation was prevented by pretreatment of the MS1 cells with a PLC inhibitor, U73122, and an intracellular Ca2+-chelating agent, BAPTA-AM. This suggests that PLC-dependent elevation of intracellular Ca2+ is involved in the SPC-induced activation of PLD. The SPC-dependent PLD activity was also almost completely prevented by pretreatment with pan-specific PKC inhibitors, GF109203X and RO-31-8220, and with a PKCdelta-specific inhibitor, rottlerin, but not by pretreatment with GO6976, a conventional PKC isozymes-specific inhibitor. Adenoviral overexpression of a kinase-deficient mutant of PKCdelta attenuated the SPC-induced PLD activity. These results suggest that PKCdelta plays a crucial role for the SPC-induced PLD activation. The SPC-induced PLD activation was preferentially potentiated in COS-7 cells transfected with PLD2 but not with PLD1, suggesting a specific implication of PLD2 in the SPC-induced PLD activation. SPC treatment induced phosphorylation of PLD2 in COS-7 cells, and overexpression of the kinase-deficient mutant of PKCdelta prevented the SPC-induced phosphorylation of PLD2. Furthermore, SPC treatment generated reactive oxygen species (ROS) in MS1 cells and the SPC induced production of ROS was inhibited by pretreatment with U73122, BAPTA-AM, and rottlerin. In addition, pretreatment with a PLD inhibitor 1-butanol and overexpression of a lipase-inactive mutant of PLD2 but not PLD1 attenuated the SPC-induced generation of ROS. These results suggest that PLC-, Ca2+-, PKCdelta-, and PLD2-dependent pathways are essentially required for the SPC induced ROS generation. 相似文献
996.
Park JY Kim HY Lee JY Kim KH Jang MK Lee JH Yoo JY Han DS Hahm JS 《FEMS immunology and medical microbiology》2005,44(2):171-176
Macrolide antibiotics have an anti-inflammatory effect by suppressing lipopolysaccharide-induced IL-8 production. IL-8 secretion from monocytes is observed in Helicobacter pylori infection. Although cag gene products are known to induce IL-8 secretion, whether other bacterial substances can initiate the reaction is not determined. In this study, we show that clarithromycin induced down-regulation of Toll-like receptor 4 expression and did not lead to a decrease in IL-8 production and H. pylori lipopolysaccharide. However, Toll-like receptor 4 activation was possibly not the main cause in the induction of inflammation during H. pylori infection. 相似文献
997.
Rhie GE Park YM Chun JH Yoo CK Seong WK Oh HB 《FEMS immunology and medical microbiology》2005,45(2):331-339
We used the Bacillus brevis-pNU212 system to develop a mass production system for the protective antigen (PA) of Bacillus anthracis. A moderately efficient expression-secretion system for PA was constructed by fusing the PA gene from B. anthracis with the B. brevis cell-wall protein signal-peptide encoding region of pNU212, and by introducing the recombinant plasmid, pNU212-mPA, into B. brevis 47-5Q. The clone producing PA secreted about 300 microg of recombinant PA (rPA) per ml of 5PY-erythromycin medium after 4 days incubation at 30 degrees C. The rPA was fractionated from the culture supernatant of B. brevis 47-5Q carrying pNU212-mPA using ammonium sulfate at 70% saturation followed by anion exchange chromatography on a Hitrap Q, a Hiload 16/60 Superdex 200 gel filtration column and a phenyl sepharose hydrophobic interaction column, yielding 70 mg rPA per liter of culture. The N-terminal sequence of the purified rPA was identical to that of native PA from B. anthracis. The purified rPA exhibited cytotoxicity towards J774A.1 cells when combined with lethal factor. The rPA formulated in either Rehydragel HPA or MPL-TDM-CWS adjuvant (Ribi-Trimix) elicited the expression of a large amount of anti-PA and neutralizing antibodies in guinea pigs and completely protected them against a 100 LD50 challenge with fully virulent B. anthracis spores. 相似文献
998.
999.
c-Jun N-terminal kinase is involved in the suppression of adiponectin expression by TNF-alpha in 3T3-L1 adipocytes 总被引:5,自引:0,他引:5
Kim KY Kim JK Jeon JH Yoon SR Choi I Yang Y 《Biochemical and biophysical research communications》2005,327(2):460-467
Adiponectin, one of adipokines that is secreted from adipocytes, plays an important role in the regulation of glucose and lipid metabolism. Paradoxically, serum concentrations of adiponectin are decreased in obese and type 2 diabetic patients, although it is produced in adipose tissue. On the other hand, plasma TNF-alpha levels are increased in such subjects. In the present study, the mechanism by which adiponectin is regulated by TNF-alpha was investigated. The decreased adiponectin mRNA levels by TNF-alpha were partially recovered by treatment with a c-Jun N-terminal kinase (JNK) inhibitor or the PPAR-gamma agonist rosiglitazone in 3T3-L1 adipocytes. Interestingly, however, cotreatment with the JNK inhibitor and rosiglitazone led to a recovery of TNF-alpha-mediated adiponectin suppression to the control level. The JNK inhibitor regulated the expression of adiponectin by the increase of PPAR-gamma DNA binding activity and the recovery of its mRNA expression while rosiglitazone acted via a PPAR-gamma independent pathway which remains to be elucidated. These findings suggest that the JNK signaling pathway, activated by TNF-alpha, is involved in the regulation of adiponectin expression. 相似文献
1000.
COX-2 regulates p53 activity and inhibits DNA damage-induced apoptosis 总被引:11,自引:0,他引:11