全文获取类型
收费全文 | 11684篇 |
免费 | 1057篇 |
国内免费 | 209篇 |
出版年
2023年 | 46篇 |
2022年 | 159篇 |
2021年 | 289篇 |
2020年 | 184篇 |
2019年 | 231篇 |
2018年 | 266篇 |
2017年 | 216篇 |
2016年 | 343篇 |
2015年 | 617篇 |
2014年 | 611篇 |
2013年 | 763篇 |
2012年 | 946篇 |
2011年 | 833篇 |
2010年 | 517篇 |
2009年 | 462篇 |
2008年 | 576篇 |
2007年 | 539篇 |
2006年 | 545篇 |
2005年 | 494篇 |
2004年 | 443篇 |
2003年 | 393篇 |
2002年 | 314篇 |
2001年 | 302篇 |
2000年 | 285篇 |
1999年 | 244篇 |
1998年 | 112篇 |
1997年 | 89篇 |
1996年 | 91篇 |
1995年 | 85篇 |
1994年 | 74篇 |
1993年 | 78篇 |
1992年 | 163篇 |
1991年 | 125篇 |
1990年 | 118篇 |
1989年 | 129篇 |
1988年 | 92篇 |
1987年 | 94篇 |
1986年 | 101篇 |
1985年 | 105篇 |
1984年 | 78篇 |
1983年 | 80篇 |
1982年 | 64篇 |
1981年 | 57篇 |
1980年 | 51篇 |
1979年 | 83篇 |
1978年 | 64篇 |
1977年 | 51篇 |
1976年 | 56篇 |
1975年 | 45篇 |
1974年 | 50篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
Roles of phosphatidylinositol 3-kinase and NF-kappaB in human cytomegalovirus-mediated monocyte diapedesis and adhesion: strategy for viral persistence 下载免费PDF全文
Smith MS Bivins-Smith ER Tilley AM Bentz GL Chan G Minard J Yurochko AD 《Journal of virology》2007,81(14):7683-7694
Infected peripheral blood monocytes are proposed to play a key role in the hematogenous dissemination of human cytomegalovirus (HCMV) to tissues, a critical step in the establishment of HCMV persistence and the development of HCMV-associated diseases. We recently provided evidence for a unique strategy involved in viral dissemination: HCMV infection of primary human monocytes promotes their transendothelial migration and differentiation into proinflammatory macrophages permissive for the replication of the original input virus. To decipher the mechanism of hematogenous spread, we focused on the viral dysregulation of early cellular processes involved in transendothelial migration. Here, we present evidence that both phosphatidylinositol 3-kinase [PI(3)K] and NF-kappaB activities were crucial for the HCMV induction of monocyte motility and firm adhesion to endothelial cells. We found that the beta(1) integrins, the beta(2) integrins, intracellular adhesion molecule 1 (ICAM-1), and ICAM-3 were upregulated following HCMV infection and that they played a key role in the firm adhesion of infected monocytes to the endothelium. The viral regulation of adhesion molecule expression is complex, with PI(3)K and NF-kappaB affecting the expression of each adhesion molecule at different stages of the expression cascade. Our data demonstrate key roles for PI(3)K and NF-kappaB signaling in the HCMV-induced cellular changes in monocytes and identify the biological rationale for the activation of these pathways in infected monocytes, which together suggest a mechanism for how HCMV promotes viral spread to and persistence within host organs. 相似文献
992.
Recent development in DNA microarray technologies has made the reconstruction of gene regulatory networks (GRNs) feasible. To infer the overall structure of a GRN, there is a need to find out how the expression of each gene can be affected by the others. Many existing approaches to reconstructing GRNs are developed to generate hypotheses about the presence or absence of interactions between genes so that laboratory experiments can be performed afterwards for verification. Since, they are not intended to be used to predict if a gene in an unseen sample has any interactions with other genes, statistical verification of the reliability of the discovered interactions can be difficult. Furthermore, since the temporal ordering of the data is not taken into consideration, the directionality of regulation cannot be established using these existing techniques. To tackle these problems, we propose a data mining technique here. This technique makes use of a probabilistic inference approach to uncover interesting dependency relationships in noisy, high-dimensional time series expression data. It is not only able to determine if a gene is dependent on another but also whether or not it is activated or inhibited. In addition, it can predict how a gene would be affected by other genes even in unseen samples. For performance evaluation, the proposed technique has been tested with real expression data. Experimental results show that it can be very effective. The discovered dependency relationships can reveal gene regulatory relationships that could be used to infer the structures of GRNs. 相似文献
993.
The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization 总被引:1,自引:0,他引:1
The evolutionarily conserved Par-3/Par-6/aPKC complex is essential for the establishment and maintenance of polarity of a wide range of cells. Both Par-3 and Par-6 are PDZ domain containing scaffold proteins capable of binding to polarity regulatory proteins. In addition to three PDZ domains, Par-3 also contains a conserved N-terminal oligomerization domain (NTD) that is essential for proper subapical membrane localization and consequently the functions of Par-3. The molecular basis of NTD-mediated Par-3 membrane localization is poorly understood. Here, we describe the structure of a monomeric form of the Par-3 NTD. Unexpectedly, the domain adopts a PB1-like fold with both type-I and type-II structural features. The Par-3 NTD oligomerizes into helical filaments via front-to-back interactions. We further demonstrate that the NTD-mediated membrane localization of Par-3 in MDCK cells is solely attributed to its oligomerization capacity. The data presented in this study suggest that the Par-3 NTD is likely to facilitate the assembly of higher-order Par-3/Par-6/aPKC complex with increased avidities in targeting the complex to the subapical membrane domain and in binding to other polarity-regulating proteins. 相似文献
994.
Aquaporin 7 is a beta-cell protein and regulator of intraislet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretion 总被引:1,自引:0,他引:1 下载免费PDF全文
Matsumura K Chang BH Fujimiya M Chen W Kulkarni RN Eguchi Y Kimura H Kojima H Chan L 《Molecular and cellular biology》2007,27(17):6026-6037
995.
Adameová A Kuzelová M Andelová E Faberová V Pancza D Svec P Ziegelhöffer A Ravingerová T 《Molecular and cellular biochemistry》2007,295(1-2):129-136
Both, diabetes mellitus (DM) and hypercholesterolemia (HCH) are known as risk factors of ischemic heart disease, however,
the effects of experimental DM, as well as of HCH alone, on ischemia/reperfusion-induced myocardial injury are not unequivocal.
We have previously demonstrated an enhanced resistance to ischemia-induced arrhythmias in rat hearts in the acute phase of
DM. Our objectives were thus to extend our knowledge on how DM in combination with HCH, a model that is relevant to diabetic
patients with altered lipid metabolism, may affect the size of myocardial infarction and susceptibility to arrhythmias. A
combination of streptozotocin (STZ; 80 mg/kg, i.p.) and the fat–cholesterol diet (1% cholesterol, 1% coconut oil; FCHD) was
used as a double-disease model mimicking DM and HCH simultaneosly occurring in humans. Following 5 days after STZ injection
and FCHD leading to increased blood glucose and cholesterol levels, anesthetized open-chest diabetic, diabetic–hypercholesterolemic
(DM–HCH) and age-matched control rats were subjected to 6-min ischemia (occlusion of LAD coronary artery) followed by 10 reperfusion
to test susceptibility to ventricular arrhythmias in the in vivo experiments and to 30-min ischemia and subsequent 2-h reperfusion for the evaluation of the infarct size (IS) in the Langendorff-perfused
hearts. The incidence of the most life-threatening ventricular arrhythmia, ventricular fibrillation, was significantly increased
in the DM–HCH rats as compared with non-diabetic control animals (100% vs. 50%; p<0.05). Likewise, arrhythmia severity score (AS) was significantly higher in the DM–HCH rats than in the controls (4.9±0.2
vs. 3.5±0.5; p<0.05), but was not increased in the diabetic animals (AS 3.7±0.9; p>0.05 vs. controls). Diabetic hearts exhibited a reduced IS (15.1±3.0% of the area at risk vs. 37.6±2.8% in the control hearts;
p<0.05), however, a combination of DM and HCH increased the size of myocardial infarction to that observed in the controls.
In conclusion, HCH abrogates enhanced resistance to ischemia-reperfusion injury in the diabetic rat heart. 相似文献
996.
Song HW Cauffman K Chan AP Zhou Y King ML Etkin LD Kloc M 《Differentiation; research in biological diversity》2007,75(6):519-528
The early development of metazoans is mainly regulated by differential translation and localization of maternal mRNAs in the embryo. In general, these processes are orchestrated by RNA-binding proteins interacting with specific sequence motifs in the 3'-untranslated region (UTR) of their target RNAs. Hermes is an RNA-binding protein, which contains a single RNA recognition motif (RRM) and is found in various vertebrate species from fish to human. In Xenopus laevis, Hermes mRNA and protein are localized in the vegetal region of oocytes. A subpopulation of Hermes protein is concentrated in a specific structure in the vegetal cortex, called the germ plasm (believed to contain determinants of the germ cell fate) where Hermes protein co-localizes with Xcat2 and RINGO/Spy mRNAs. The level of total Hermes protein decreases during maturation. The precocious depletion of Hermes protein by injection of Hermes antisense morpholino oligonucleotide (HE-MO) accelerates the process of maturation and results in cleavage defects in vegetal blastomeres of the embryo. It is known that several maternal mRNAs including RINGO/Spy and Mos are regulated at the translational level during meiotic maturation and early cleavage in Xenopus. The ectopic expression of RINGO/Spy or Mos causes resumption of meiotic maturation and cleavage arrests, which resemble the loss of Hermes phenotypes. We found that the injection of HE-MO enhances the acceleration of maturation caused by the injection of RINGO/Spy mRNA, and that Hermes protein is present as mRNP complex containing RINGO/Spy, Mos, and Xcat2 mRNAs in vivo. We propose that as an RNA-binding protein, Hermes may be involved in maturation, cleavage events at the vegetal pole and germ cell development by negatively regulating the expression of RINGO/Spy, Mos, and Xcat2 mRNAs. 相似文献
997.
Jing Che Junfeng Pang Hui Zhao Guan-fu Wu Er-mi Zhao Ya-ping Zhang 《Biochemical Systematics and Ecology》2007
The phylogeny of representative species of Chinese ranids was reconstructed using two nuclear (tyrosinase and rhodopsin) and two mitochondrial (12S rRNA, 16S rRNA) DNA fragments. Maximum parsimony, Bayesian, and maximum likelihood analyses were employed. In comparison with the results from nuclear and mitochondrial data, we used nuclear gene data as our preferred phylogenetic hypothesis. We proposed two families (Ranidae, Dicroglossidae) for Chinese ranids, with the exception of genus Ingerana. Within Dicroglossidae, four tribes were supported including Dicroglossini, Paini, Limnonectini, and Occidozygini. A broader sampling strategy and evidence from additional molecular markers are required to decisively evaluate the evolutionary history of Chinese ranids. 相似文献
998.
999.
1000.