全文获取类型
收费全文 | 18357篇 |
免费 | 1363篇 |
国内免费 | 370篇 |
专业分类
20090篇 |
出版年
2024年 | 35篇 |
2023年 | 122篇 |
2022年 | 356篇 |
2021年 | 518篇 |
2020年 | 374篇 |
2019年 | 473篇 |
2018年 | 558篇 |
2017年 | 496篇 |
2016年 | 712篇 |
2015年 | 1065篇 |
2014年 | 1226篇 |
2013年 | 1359篇 |
2012年 | 1665篇 |
2011年 | 1602篇 |
2010年 | 1017篇 |
2009年 | 850篇 |
2008年 | 1153篇 |
2007年 | 1014篇 |
2006年 | 862篇 |
2005年 | 774篇 |
2004年 | 783篇 |
2003年 | 607篇 |
2002年 | 488篇 |
2001年 | 304篇 |
2000年 | 263篇 |
1999年 | 255篇 |
1998年 | 130篇 |
1997年 | 91篇 |
1996年 | 68篇 |
1995年 | 76篇 |
1994年 | 68篇 |
1993年 | 54篇 |
1992年 | 86篇 |
1991年 | 87篇 |
1990年 | 60篇 |
1989年 | 59篇 |
1988年 | 41篇 |
1987年 | 26篇 |
1986年 | 30篇 |
1985年 | 36篇 |
1984年 | 19篇 |
1983年 | 18篇 |
1982年 | 15篇 |
1980年 | 20篇 |
1979年 | 19篇 |
1977年 | 18篇 |
1975年 | 16篇 |
1974年 | 17篇 |
1970年 | 12篇 |
1969年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Lee BH Park SY Kang KB Park RW Kim IS 《Biochemical and biophysical research communications》2002,291(5):1218-1224
Resveratrol (RSVL), an edible polyphenolic stilbene, claims a myriad of cardiovascular benefits. However, the molecular underpinnings of such actions are poorly understood. Currently, in sheep coronary arteries (SCA), RSVL markedly (threefold) enhanced cGMP formation (t(1/2): 6.5 min; EC(50): 3 microM). This response was not abrogated by the phosphodiesterase inhibitor (IBMX, 0.5 mM), but was partly sensitive (20-30%) to either removal of the endothelium, treatment with the nitric oxide synthase-inhibitor (L-NMMA, 10 microM), or with the soluble GC (sGC)-inhibitor (ODQ, 10 microM). In membrane preparations from denuded SCA, either RSVL or the pGC agonist atrial natriuretic peptide (ANP, 0.1-1 microM) activated GC in the particulate, but not in the soluble, membrane fraction. By contrast, the nitric oxide donor, sodium nitroprusside (SNP, 1-10 microM), stimulated GC only in the soluble fraction. Further, pretreatment with RSVL partly desensitized the ANP response, but was additive to that of SNP. In arterial tension studies, RSVL relaxed PGF(2alpha)-precontracted denuded rings in a concentration-dependent manner, a response that was markedly enhanced (approximately 18 fold) in the presence of IBMX. Conversely, precontraction with phorbol ester, which also desensitizes pGC, blunted relaxations to RSVL but not to forskolin or SNP. These findings demonstrate that RSVL increases cGMP in coronary arteries, mostly by activation of pGC. This pathway triggers vasorelaxant responses that remain effective in endothelium-disrupted arteries. 相似文献
992.
Bahn JH Kim AY Jang SH Lee BR Ahn JY Joo HM Kan TC Won MH Kwon HY Kang JH Kwon OS Kim HB Cho SW Lee KS Park J Choi SY 《Molecules and cells》2002,13(1):21-27
Five monoclonal antibodies that recognize porcine brain myo-inositol monophosphate phosphatase (IMPase) have been selected and designated as mAb IMPP 9, IMPP 10, IMPP 11, IMPP 15, and IMPP 17. These antibodies recognize different epitopes of the enzyme and one of these inhibited the enzyme activity. When the total proteins of the porcine brain homogenate separated by SDS-PAGE were probed with monoclonal antibodies, a single reactive protein band of 29 kDa, co-migrating with the purified porcine brain IMPase, was detected. Using the anti-IMPase antibodies as probes, the cross reactivities of the brain IMPase from human and other mammalian tissues, as well as from avian sources, were investigated. Among the human and animal tissues tested, the immunoreactive bands on Western blots appeared to have the same molecular mass of 29 kDa. In addition, there was IMPase immunoreactivity in the various neuronal populations in the rat brain. These results indicate that mammalian brains contain only one major type of immunologically similar IMPase, although some properties of the enzymes that were previously reported differ from each another. The first demonstration of the IMPase localization in the brain may also provide useful data for future investigations on the function of this enzyme in relation to various neurological diseases. 相似文献
993.
Lack of Sequence Homology Among RNAs of Avian Leukosis-Sarcoma Viruses, Reticuloendotheliosis Viruses, and Chicken Endogenous RNA-Directed DNA Polymerase Activity 总被引:7,自引:41,他引:7 下载免费PDF全文
The relatedness of the RNAs of the three avian systems, including six avian leukosis-sarcoma viruses, four reticuloendotheliosis viruses, and the microsome fraction of normal uninfected chicken embryo cells, containing RNA and a DNA polymerase have been studied by nucleic acid hybridization. All six avian leukosis-sarcoma viruses have closely related nucleotide sequences; and all four reticuloendotheliosis viruses have closely related nucleotide sequences. But, almost no similarities were detected between the RNAs of avian leukosis-sarcoma viruses and reticuloendotheliosis viruses. The RNA template of the endogenous RNA-directed DNA polymerase activity of normal uninfected chicken cells had no detectable relationship to RNAs of avian leukosis-sarcoma and reticuloendotheliosis viruses. 相似文献
994.
Jong Seok Lee Ki Rim Lee Sarah Lee Hye Jin Lee Hee-sun Yang Joohong Yeo Jun Myoung Park Byung Hyun Choi Eock Kee Hong 《Biotechnology and Bioprocess Engineering》2017,22(1):45-51
Polysaccharides isolated from Inonotus obliquus (PLIO) have been known to have various pharmacological activities including antioxidant, immunostimulating and anti-tumor activity. However, the anti-metastatic effect of PLIO in human non-small cell lung carcinoma (NSCLC) has not been elucidated. In this study, we investigated the effects of PLIO on the metastatic potential of human NSCLC A549 cells and its underlying mechanisms. PLIO suppressed the invasive potential of A549 cells throughout reducing matrix metalloproteinase (MMP) expression. PLIO treatment inhibited NF-κB nuclear translocation in A549 cells. In addition, PLIO treatment inhibited the phosphorylation of JNK/AKT in A549 cells. These results suggest that PLIO could inhibit human NSCLC invasion via suppression of AKT/NF-κB signaling pathway. 相似文献
995.
MacDonald PE Wang G Tsuk S Dodo C Kang Y Tang L Wheeler MB Cattral MS Lakey JR Salapatek AM Lotan I Gaisano HY 《Molecular endocrinology (Baltimore, Md.)》2002,16(11):2452-2461
Insulin secretion is initiated by ionic events involving membrane depolarization and Ca(2+) entry, whereas exocytic SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins mediate exocytosis itself. In the present study, we characterize the interaction of the SNARE protein SNAP-25 (synaptosome-associated protein of 25 kDa) with the beta-cell voltage-dependent K(+) channel Kv2.1. Expression of Kv2.1, SNAP-25, and syntaxin 1A was detected in human islet lysates by Western blot, and coimmunoprecipitation studies showed that heterologously expressed SNAP-25 and syntaxin 1A associate with Kv2.1. SNAP-25 reduced currents from recombinant Kv2.1 channels by approximately 70% without affecting channel localization. This inhibitory effect could be partially alleviated by codialysis of a Kv2.1N-terminal peptide that can bind in vitro SNAP-25, but not the Kv2.1C-terminal peptide. Similarly, SNAP-25 blocked voltage-dependent outward K(+) currents from rat beta-cells by approximately 40%, an effect that was completely reversed by codialysis of the Kv2.1N fragment. Finally, SNAP-25 had no effect on outward K(+) currents in beta-cells where Kv2.1 channels had been functionally knocked out using a dominant-negative approach, indicating that the interaction is specific to Kv2.1 channels as compared with other beta-cell Kv channels. This study demonstrates that SNAP-25 can regulate Kv2.1 through an interaction at the channel N terminus and supports the hypothesis that SNARE proteins modulate secretion through their involvement in regulation of membrane ion channels in addition to exocytic membrane fusion. 相似文献
996.
Reprogramming of the activity of the activator/dissociation transposon family during plant regeneration in rice 总被引:3,自引:0,他引:3
Ki CM Je BI Piao HL Par SJ Kim MJ Park SH Park JY Park SH Lee EK Chon NS Won YJ Lee GH Nam MH Yun DW Lee MC Cha YS Le Kon H Eun MY Han CD 《Molecules and cells》2002,14(2):231-237
Many aspects of epigenetic phenomena have been elucidated via studies of transposable elements. An active transposable element frequently loses its ability to mobilize and goes into an inactive state during development. In this study, we describe the cyclic activity of a maize transposable element dissociation (Ds) in rice. In rice genome, Ds undergoes the spontaneous loss of mobility. However, an inactive state of Ds can be changed into an active state during tissue culture. The recovery of mobility accompanies not only changes in the methylation patterns of the terminal region of Ds, but also alteration in the steady state level of the activator (Ac) mRNA that is expressed by a constitutive CaMV 35S promoter. Furthermore, the Ds-reactivation process is not random, but stage-specific during plantlet regeneration. Our findings have expanded previous observations on Ac reactivation in the tissue culture of maize. 相似文献
997.
Timur Yagudin Yue Zhao Haiyu Gao Yang Zhang Ying Yang Xiaofang Zhang Wenbo Ma Tolessa Muleta Daba Vladimir Ishmetov Kai Kang Baofeng Yang Zhenwei Pan 《Acta biochimica et biophysica Sinica》2021,(1):102-111
Currently, there remains a great need to elucidate the molecular mechanism of acute myocardial infarction in order to facilitate the development of novel therapy. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member of the ASPP family proteins and an evolutionarily preserved inhibitor of p53 that is involved in many cellular processes, including apoptosis of cancer cells. The purpose of this study was to investigate the possible role of iASPP in acute myocardial infarction. The protein level of iASPP was markedly reduced in the ischemic hearts in vivo and hydrogen peroxide-exposed cardiomyocytes in vitro. Overexpression of iASPP reduced the infarct size and cardiomyocyte apoptosis of mice subjected to 24 h of coronary artery ligation. Echocardiography showed that cardiac function was improved as indicated by the increase in ejection fraction and fractional shortening. In contrast, knockdown of iASPP exacerbated cardiac injury as manifested by impaired cardiac function, increased infarct size, and apoptosis rate. Mechanistically, overexpression of iASPP inhibited, while knockdown of iASPP increased the expressions of p53 and Bax, the key regulators of apoptosis. Taken together, our results suggested that iASPP is an important regulator of cardiomyocyte apoptosis, which represents a potential target in the therapy of myocardial infarction. 相似文献
998.
An DS Cui CH Sung BH Yang HC Kim SC Lee ST Im WT Kim SG 《Applied microbiology and biotechnology》2012,94(3):673-682
The gene encoding an α-l-arabinofuranosidase that could biotransform ginsenoside Rc {3-O-[β-d-glucopyranosyl-(1–2)-β-d-glucopyranosyl]-20-O-[α-l-arabinofuranosyl-(1–6)-β-d-glucopyranosyl]-20(S)-protopanaxadiol} to ginsenoside Rd {3-O-[β-d-glucopyranosyl-(1–2)-β-d-glucopyranosyl]-20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol} was cloned from a soil bacterium, Rhodanobacter ginsenosidimutans strain Gsoil 3054T, and the recombinant enzyme was characterized. The enzyme (AbfA) hydrolyzed the arabinofuranosyl moiety from ginsenoside
Rc and was classified as a family 51 glycoside hydrolase based on amino acid sequence analysis. Recombinant AbfA expressed
in Escherichia coli hydrolyzed non-reducing arabinofuranoside moieties with apparent K
m values of 0.53 ± 0.07 and 0.30 ± 0.07 mM and V
max values of 27.1 ± 1.7 and 49.6 ± 4.1 μmol min−1 mg−1 of protein for p-nitrophenyl-α-l-arabinofuranoside and ginsenoside Rc, respectively. The enzyme exhibited preferential substrate specificity of the exo-type
mode of action towards polyarabinosides or oligoarabinosides. AbfA demonstrated substrate-specific activity for the bioconversion
of ginsenosides, as it hydrolyzed only arabinofuranoside moieties from ginsenoside Rc and its derivatives, and not other sugar
groups. These results are the first report of a glycoside hydrolase family 51 α-l-arabinofuranosidase that can transform ginsenoside Rc to Rd. 相似文献
999.
Ruining Wang Hongfang Ma Yinfeng Kang Cunfa Li Huawei Li Erqin Zhang Pengchao Ji Jian He Mengmeng Zhao 《Indian journal of microbiology》2018,58(3):332-344
An interferon-mediated antiviral protein, 2′–5′ oligoadenylate synthetase 2, plays an important role in the antiviral response of interferons. In this study, 2′–5′ oligoadenylate synthetase 2 genes were cloned from Chinese domestic pigs. Bioinformatics analysis revealed that the 2024-bp long open reading fame encodes 707 amino acids. There are two conserved regions in this protein: the nucleotidyltransferase domain, and the 2′–5′ oligoadenylate synthetase domain (OAS). Genetic evolution analysis showed that the 2′–5′ oligoadenylate synthetase 2 gene in domestic pigs is closely related to that of cattle. There are multiple antigenic sites, no signal peptide, and no transmembrane region in the gene, which is predicted to be a hydrophilic protein. Secondary structures were found to be mainly alpha helix-based; its tertiary structure is close to that of humans and cattle, but not that of mice. Tissue distribution results indicated that this protein is distributed in multiple organs, with high distribution in the liver; it is mainly localized in the cytoplasm. PRRSV infection, interferon-beta, and Poly(I: C) treatment all promoted 2′–5′ oligoadenylate synthetase 2 gene expression. Overexpression and RNA silencing of porcine OAS2 inhibited and promoted PRRSV replication in cells, respectively. The inhibitory effect of porcine OAS2 was mainly dependent on RNase L, similar to what was predicted. This study has laid the foundation for future antiviral studies in pig, and provided a new way of preventing and treating PRRSV in the future. 相似文献
1000.
Kyungsu Kang Lei Peng Yu-Jin Jung Joo Yeon Kim Eun Ha Lee Hee Ju Lee Sang Min Kim Sang Hyun Sung Cheol-Ho Pan Yongsoo Choi 《Biotechnology letters》2018,40(2):263-270