全文获取类型
收费全文 | 48657篇 |
免费 | 4327篇 |
国内免费 | 5132篇 |
专业分类
58116篇 |
出版年
2024年 | 160篇 |
2023年 | 771篇 |
2022年 | 1576篇 |
2021年 | 2474篇 |
2020年 | 1735篇 |
2019年 | 2268篇 |
2018年 | 2042篇 |
2017年 | 1526篇 |
2016年 | 2186篇 |
2015年 | 3081篇 |
2014年 | 3740篇 |
2013年 | 3833篇 |
2012年 | 4638篇 |
2011年 | 4231篇 |
2010年 | 2670篇 |
2009年 | 2372篇 |
2008年 | 2770篇 |
2007年 | 2462篇 |
2006年 | 2090篇 |
2005年 | 1835篇 |
2004年 | 1568篇 |
2003年 | 1485篇 |
2002年 | 1334篇 |
2001年 | 789篇 |
2000年 | 710篇 |
1999年 | 665篇 |
1998年 | 437篇 |
1997年 | 392篇 |
1996年 | 337篇 |
1995年 | 263篇 |
1994年 | 283篇 |
1993年 | 178篇 |
1992年 | 233篇 |
1991年 | 182篇 |
1990年 | 168篇 |
1989年 | 129篇 |
1988年 | 98篇 |
1987年 | 65篇 |
1986年 | 60篇 |
1985年 | 81篇 |
1984年 | 39篇 |
1983年 | 44篇 |
1982年 | 32篇 |
1981年 | 13篇 |
1980年 | 5篇 |
1979年 | 12篇 |
1977年 | 5篇 |
1975年 | 5篇 |
1971年 | 4篇 |
1965年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
Liu Q Chen J Liu L Zhang J Wang D Ma L He Y Liu Y Liu Z Wu J 《The Journal of biological chemistry》2011,286(19):17168-17180
The X protein (HBx) of hepatitis B virus (HBV) is involved in the development of hepatocellular carcinoma (HCC), and methionine adenosyltransferase 2A (MAT2A) promotes the growth of liver cancer cells through altering S-adenosylmethionine homeostasis. Thus, we speculated that a link between HBx and MAT2A may contribute to HCC development. In this study, the effects of HBx on MAT2A expression and cell apoptosis were investigated, and the molecular mechanism by which HBx and MAT2A regulate tumorigenesis was evaluated. Results from immunohistochemistry analyses of 37 pairs of HBV-associated liver cancer tissues/corresponding peritumor tissues showed that HBx and MAT2A are highly expressed in most liver tumor tissues. Our in vitro results revealed that HBx activates MAT2A expression in a dose-dependent manner in hepatoma cells, and such regulation requires the cis-regulatory elements NF-κB and CREB on the MAT2A gene promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) further demonstrated that HBx facilitates the binding of NF-κB and CREB to MAT2A gene promoter. In addition, overexpression of HBx or MAT2A inhibits cell apoptosis, whereas knockdown of MAT2A expression stimulates apoptosis in hepatoma cells. Furthermore, we demonstrated that HBx reduces MAT1A expression and AdoMet production but enhances MAT2β expression. Thus, we proposed that HBx activates MAT2A expression through NF-κB and CREB signaling pathways to reduce AdoMet production, inhibit hepatoma cell apoptosis, and perhaps enhance HCC development. These findings should provide new insights into our understanding how the molecular mechanisms underline the effects of HBV infection on the production of MAT2A and the development of HCC. 相似文献
993.
Jeong KC Kang MY Kang J Baumler DJ Kaspar CW 《Applied and environmental microbiology》2011,77(8):2611-2616
Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a significant human pathogen that resides in healthy cattle. It is thought that a reduction in the prevalence and numbers of EHEC in cattle will reduce the load of EHEC entering the food chain. To this end, an intervention strategy involving the addition of chitosan microparticles (CM) to feed in order to reduce the carriage of this pathogen in cattle was evaluated. Experiments with individual Holstein calves and a crossover study found that the addition of CM to feed decreased E. coli O157:H7 shedding. In the crossover study, CM resulted in statistically significant reductions in the numbers recovered from rectal swab samples (P < 0.05) and the duration of shedding (P < 0.05). The effects of feeding CM to calves differed, indicating that the optimal levels of CM may differ between animals or that other factors are involved in the interaction between CM and E. coli O157:H7. In vitro studies demonstrated that E. coli O157:H7 binds to CM, suggesting that the reduction in shedding may result at least in part from the binding of positively charged CM to negatively charged E. coli cells. Additional studies are needed to determine the impact of CM feeding on animal production, but the results from this study indicate that supplementing feed with CM reduces the shedding of E. coli O157:H7 in cattle. 相似文献
994.
Seung Pil Yun Jung Min Ryu Min Woo Jang Ho Jae Han 《Journal of cellular physiology》2011,226(2):559-571
Although many previous reports have examined the function of prostaglandin E2 (PGE2) in the migration and proliferation of various cell types, the role of the actin cytoskeleton in human mesenchymal stem cells (hMSCs) migration and proliferation has not been reported. The present study examined the involvement of profilin‐1 (Pfn‐1) and filamentous‐actin (F‐actin) in PGE2‐induced hMSC migration and proliferation and its related signal pathways. PGE2 (10?6 M) increased both cell migration and proliferation, and also increased E‐type prostaglandin receptor 2 (EP2) mRNA expression, β‐arrestin‐1 phosphorylation, and c‐Jun N‐terminal kinase (JNK) phosphorylation. Small interfering RNA (siRNA)‐mediated knockdown of β‐arrestin‐1 and JNK (‐1, ‐2, ‐3) inhibited PGE2‐induced growth of hMSCs. PGE2 also activated Pfn‐1, which was blocked by JNK siRNA, and induced F‐actin level and organization. Downregulation of Pfn‐1 by siRNA decreased the level and organization of F‐actin. In addition, specific siRNA for TRIO and F‐actin‐binding protein (TRIOBP) reduced the PGE2‐induced increase in hMSC migration and proliferation. Together, these experimental data demonstrate that PGE2 partially stimulates hMSCs migration and proliferation by interaction of Pfn‐1 and F‐actin via EP2 receptor‐dependent β‐arrestin‐1/JNK signaling pathways. J. Cell. Physiol. 226: 559–571, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
995.
Electric fields, generated by active transport of ions, are present in many biological systems and often serve important functions in tissues and organs. For example, they play an important role in directing cell migration during wound healing. Here we describe the manufacture and use of ultrasensitive vibrating probes for measuring extracellular electric currents. The probe is an insulated, sharpened metal wire with a small platinum-black tip (30-35 μm), which can detect ionic currents in the μA/cm2 range in physiological saline. The probe is vibrated at about 200 Hz by a piezoelectric bender. In the presence of an ionic current, the probe detects a voltage difference between the extremes of its movement. A lock-in amplifier filters out extraneous noise by locking on to the probe''s frequency of vibration. Data are recorded onto computer. The probe is calibrated at the start and end of experiments in appropriate saline, using a chamber which applies a current of exactly 1.5 μA/cm2. We describe how to make the probes, set up the system and calibrate. We also demonstrate the technique of cornea measurement, and show some representative results from different specimens (cornea, skin, brain).Download video file.(47M, mov) 相似文献
996.
Assay of L-3-hydroxyacyl-coenzyme A dehydrogenase with substrates of different chain lengths 总被引:1,自引:0,他引:1
A method for assaying L-3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) which permits rate measurements with L-3-hydroxyacyl-CoA substrates of various chain lengths at physiological pH is described. The method is based on a coupled assay system in which 3-ketoacyl-CoA compounds formed by the dehydrogenase are cleaved by 3-ketoacyl-CoA thiolase (EC 2.3.1.16) in the presence of CoASH. The advantages of this assay method are its irreversibility and elimination of product inhibition. The assay procedure was used to determine the kinetic parameters (Km, Vmax) of pig heart L-3-hydroxyacyl-CoA dehydrogenase with several substrates of various chain lengths. The data obtained show the enzyme to be most active with medium-chain substrates whereas Km values for medium-chain and long-chain substrates are almost equal but much lower than those previously reported. 相似文献
997.
Yi Sun Douglas Zhou Aaditya V. Rangan David Cai 《Journal of computational neuroscience》2010,28(2):247-266
We present a numerical analysis of the dynamics of all-to-all coupled Hodgkin-Huxley (HH) neuronal networks with Poisson spike inputs. It is important to point out that, since the dynamical vector of the system contains discontinuous variables, we propose a so-called pseudo-Lyapunov exponent adapted from the classical definition using only continuous dynamical variables, and apply it in our numerical investigation. The numerical results of the largest Lyapunov exponent using this new definition are consistent with the dynamical regimes of the network. Three typical dynamical regimes—asynchronous, chaotic and synchronous, are found as the synaptic coupling strength increases from weak to strong. We use the pseudo-Lyapunov exponent and the power spectrum analysis of voltage traces to characterize the types of the network behavior. In the nonchaotic (asynchronous or synchronous) dynamical regimes, i.e., the weak or strong coupling limits, the pseudo-Lyapunov exponent is negative and there is a good numerical convergence of the solution in the trajectory-wise sense by using our numerical methods. Consequently, in these regimes the evolution of neuronal networks is reliable. For the chaotic dynamical regime with an intermediate strong coupling, the pseudo-Lyapunov exponent is positive, and there is no numerical convergence of the solution and only statistical quantifications of the numerical results are reliable. Finally, we present numerical evidence that the value of pseudo-Lyapunov exponent coincides with that of the standard Lyapunov exponent for systems we have been able to examine. 相似文献
998.
Jian Huang Ding Tang Yi Shen Baoxiang Qin Lilan Hong Aiqing You Ming Li Xin Wang Hengxiu Yu Minghong Gu Zhukuan Cheng 《遗传学报》2010,37(1):23-36
Gibberellin (GA) 2-oxidase plays a key role in the GA catabolic pathway through 2β-hydroxylation.In the present study,we isolated a CaMV 35S-enhancer activation tagged mutant,H032.This mutant exhibited a dominant dwarf and GA-deficient phenotype,with a final stature that was less than half of its wild-type counterpart.The endogenous bioactive GAs are markedly decreased in the H032 mutant,and application of bioactive GAs (GA3 or GA4) can reverse the dwarf phenotype.The integrated T-DNA was detected 12.8 kb upstream of the OsGA2ox6 in the H032 genome by TAIL-PCR.An increased level of OsGA2ox6 mRNA was detected at a high level in the H032 mutant,which might be due to the enhancer role of the CaMV 35S promoter.RNAi and ectopic expression analysis of OsGA2ox6 indicated that the dwarf trait and the decreased levels of bioactive GAs in the H032 mutant were a result of the up-regulation of the OsGA2ox6 gene.BLASTP analysis revealed that OsGA2ox6 belongs to the class III of GA 2-oxidases,which is a novel type of GA2ox that uses C20-GAs (GA12 and/or GA53) as the substrates.Interestingly,we found that a GA biosynthesis inhibitor,paclobutrazol,positively regulated the OsGA2ox6 gene.Unlike the over-expression of OsGA2ox1,which led to a high rate of seed abortion,the H032 mutant retained normal flowering and seed production.These results indicate that OsGA2ox6 mainly affects plant stature,and the dominant dwarf trait of the H032 mutant can be used as an efficient dwarf resource in rice breeding. 相似文献
999.
β-Adrenergic receptors can activate extracellular signal-regulated kinases (ERKs) via different mechanisms. In this study,
we investigated the molecular mechanism of β1-adrenergic receptor (β1AR)-mediated ERK activation in African green monkey kidney
COS-7 cells. Treatment of cells with isoproterenol (ISO), a β1AR selective agonist, induced phosphorylation of ERK1/2 in a
dose-dependent manner. ISO-stimulated ERK phosphorylation was not influenced by the Gβγ inhibitor, βAR kinase carboxyl terminal
(βARKct) or by the Gi inhibitor, pertussis toxin (PTX), but it was clearly abolished via inhibition of protein kinase A (PKA)
with H89, or of mitogen-activated protein kinase kinase (MEK1) with PD98059, revealing that the Gαs subunit is involved in
ERK regulation through the PKA/MEK1 pathway. We also tested the effect of the adenylate cyclase activator forskolin on ERK
activation, and the result was identical to that of ISO stimulation. Moreover, pretreatment with the epidermal growth factor
receptor (EGFR) tyrosine kinase inhibitor AG1478 or with the Src tyrosine kinase inhibitor PP2 did not affect ERK activation.
These observations suggest a mechanism of β1AR-mediated ERK activity that involves the Gαs subunit, but not EGFR or Src tyrosine
kinase. 相似文献
1000.
Xiaoxing You Liangzhuan Liu Yanhua Zeng Ranhui Li Jun He Xiaohua Ma Chuanhao Jiang Cuiming Zhu Liesong Chen Minjun Yu Guangli Ou Yimou Wu 《PloS one》2014,9(7)