全文获取类型
收费全文 | 3387篇 |
免费 | 205篇 |
国内免费 | 3篇 |
出版年
2023年 | 22篇 |
2022年 | 49篇 |
2021年 | 108篇 |
2020年 | 64篇 |
2019年 | 86篇 |
2018年 | 71篇 |
2017年 | 85篇 |
2016年 | 103篇 |
2015年 | 147篇 |
2014年 | 192篇 |
2013年 | 262篇 |
2012年 | 319篇 |
2011年 | 255篇 |
2010年 | 178篇 |
2009年 | 155篇 |
2008年 | 180篇 |
2007年 | 227篇 |
2006年 | 163篇 |
2005年 | 157篇 |
2004年 | 144篇 |
2003年 | 115篇 |
2002年 | 109篇 |
2001年 | 38篇 |
2000年 | 47篇 |
1999年 | 25篇 |
1998年 | 26篇 |
1997年 | 19篇 |
1996年 | 24篇 |
1995年 | 22篇 |
1994年 | 14篇 |
1993年 | 14篇 |
1992年 | 18篇 |
1991年 | 13篇 |
1990年 | 12篇 |
1989年 | 16篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1972年 | 5篇 |
1971年 | 7篇 |
1969年 | 4篇 |
1968年 | 6篇 |
1966年 | 4篇 |
排序方式: 共有3595条查询结果,搜索用时 15 毫秒
41.
42.
Itziar Lanas Piedad Gallego Luisa Martin Javier Fernandez Angel Alonso Juana Elena-Rosello Antonio Blazquez Nieves Villalobos Hilario Guerra 《Plant Growth Regulation》2006,49(1):49-60
High production of viable somatic embryos was obtained from cultured anthers in the second phase of meiosis, using microscopic
level observations of tetrads. The medium with the greatest embryogenic efficiency was H6, composed of Murashige and Skoog
(MS) medium with 2 mg l−1 of 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.5 mg l−1 of kinetin. All (100%) of the somatic embryos obtained germinated and produced 63% green and 37% albino seedlings. In general,
embryogenic calli had a higher ion concentration than non-embryogenic calli, with the exception of calcium whose concentration
was higher in non-embryogenic calli. The calli induced in the different media differed in their sucrose and starch compositions.
The most embryogenic medium H6-induced calli with the highest sucrose concentration and the lowest starch concentration, before
visible embryos were observed. In the leaves of the albino seedlings, sucrose concentrations were very high while those of
starch were very low. Ion concentrations were also lower in albino plants than in the leaves of green seedlings, with the
exception of calcium, whose concentration was higher. Most of the albino individuals were homozygous, even when their progenitors
were heterozygous, thereby confirming their haploid nature. 相似文献
43.
Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action 总被引:14,自引:0,他引:14
下载免费PDF全文
![点击此处可从《Microbiological reviews》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M. A. García J. Gil I. Ventoso S. Guerra E. Domingo C. Rivas M. Esteban 《Microbiological reviews》2006,70(4):1032-1060
44.
45.
Conlon JM Al-Ghaferi N Abraham B Sonnevend A Coquet L Leprince J Jouenne T Vaudry H Iwamuro S 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2006,143(1):42-49
The Tsushima brown frog Rana tsushimensis Stejneger, 1907 exists in reproductive isolation on the island of Tsushima, Japan. Six peptides with antimicrobial activity were isolated in pure form from an extract of the skin of this species and their amino acid sequences identified them as members of the brevinin-1 (one peptide), brevinin-2 (one peptide) and temporin (four peptides) families. The C-terminally alpha-amidated brevinin-1 peptide (FLGSIVGALASALPSLISKIRN.NH2) lacks the cyclic heptapeptide domain Cys18-(Xaa)4-Lys-Cys24 at the COOH-terminus of the molecule that characterizes other members of that family. A structurally similar brevinin-1 peptide, also lacking the cyclic domain, was previously isolated from the skin of the Ryukyu brown frog Rana okinavana, indicative of a close phylogenetic relationship between the species. Brevinin-2TSa (GIMSLFKGVLKTAGKHVAGSLVDQLKCKITGGC) showed broad-spectrum growth inhibitory activity against a range of Gram-negative and Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus) (minimum inhibitory concentrations< or =25 microM) and relatively low hemolytic activity against human erythrocytes (LD50=100 microM). The peptide therefore represents a candidate for drug development. 相似文献
46.
Petitdemange C Becquart P Wauquier N Béziat V Debré P Leroy EM Vieillard V 《PLoS pathogens》2011,7(9):e1002268
Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-γ production. Collectively these data provide insight into the role of this unique subset of NK cells in controlling CHIKV infection by subset-specific expansion in response to acute infection, followed by a contraction phase after viral clearance. 相似文献
47.
Tinto N Zagari A Capuano M De Simone A Capobianco V Daniele G Giugliano M Spadaro R Franzese A Sacchetti L 《PloS one》2008,3(4):e1870
Background
Maturity onset diabetes of the young type 2 (or GCK MODY) is a genetic form of diabetes mellitus provoked by mutations in the glucokinase gene (GCK).Methodology/Principal Findings
We screened the GCK gene by direct sequencing in 30 patients from South Italy with suspected MODY. The mutation-induced structural alterations in the protein were analyzed by molecular modeling. The patients'' biochemical, clinical and anamnestic data were obtained. Mutations were detected in 16/30 patients (53%); 9 of the 12 mutations identified were novel (p.Glu70Asp, p.Phe123Leu, p.Asp132Asn, p.His137Asp, p.Gly162Asp, p.Thr168Ala, p.Arg392Ser, p.Glu290X, p.Gln106_Met107delinsLeu) and are in regions involved in structural rearrangements required for catalysis. The prevalence of mutation sites was higher in the small domain (7/12: ∼59%) than in the large (4/12: 33%) domain or in the connection (1/12: 8%) region of the protein. Mild diabetic phenotypes were detected in almost all patients [mean (SD) OGTT = 7.8 mMol/L (1.8)] and mean triglyceride levels were lower in mutated than in unmutated GCK patients (p = 0.04).Conclusions
The prevalence of GCK MODY is high in southern Italy, and the GCK small domain is a hot spot for MODY mutations. Both the severity of the GCK mutation and the genetic background seem to play a relevant role in the GCK MODY phenotype. Indeed, a partial genotype-phenotype correlation was identified in related patients (3 pairs of siblings) but not in two unrelated children bearing the same mutation. Thus, the molecular approach allows the physician to confirm the diagnosis and to predict severity of the mutation. 相似文献48.
Francisco Javier Hernandez-Blazquez Ricardo Romão Guerra José Roberto Kfoury Jr Pedro Primo Bombonato Bruno Cogliati José Roberto Machado Cunha da Silva 《Polar Biology》2006,29(10):831-836
Absorption of lipids by the enterocytes of Notothenia coriiceps, an omnivorous Antarctic and subAntarctic fish, was studied by light and electron microscopy. The lipids are absorbed by the anterior and middle intestine segments. They appear as fat droplets that measure from 0.5 to 7 μm of diameter and which accumulate in the apical cytoplasm within the first 24 h and seem to be the main fat storage form in the enterocytes. Fat is also observed as lipid particles with 60–300 nm inside the rough endoplasmic reticulum and cytoplasmic smooth vesicles. The epithelial intercellular space and the mucosal inner lamina contain lipid particles, which probably are the fat transport form. Our observations show that an intense lipid absorptive process takes place in N. coriiceps digestive system, due to the great extension of the intestine involved and due to the great lipid accumulation found in the epithelial compartment. 相似文献
49.
Acosta-Rivero N Rodriguez A Musacchio A Falcón V Suarez VM Martinez G Guerra I Paz-Lago D Morera Y de la Rosa MC Morales-Grillo J Dueñas-Carrera S 《Biochemical and biophysical research communications》2004,325(1):68-74
Different variants of hepatitis C virus core protein (HCcAg) have proved to self-assemble in vitro into virus-like particles (VLPs). However, difficulties in obtaining purified mature HCcAg have limited these studies. In this study, a high degree of monomeric HCcAg purification was accomplished using chromatographic procedures under denaturing conditions. Size exclusion chromatography and sucrose density gradient centrifugation of renatured HCcAg (in the absence of structured RNA) under reducing conditions suggested that it assembled into empty capsids. The electron microscopy analysis of renatured HCcAg showed the presence of spherical VLPs with irregular shapes and an average diameter of 35nm. Data indicated that HCcAg monomers assembled in vitro into VLPs in the absence of structured RNA, suggesting that recombinant HCcAg used in this work contains all the information necessary for the assembly process. However, they also suggest that some cellular factors might be required for the proper in vitro assembly of capsids. 相似文献
50.
Simon Schafferer Rimpi Khurana Violetta Refolo Serena Venezia Edith Sturm Paolo Piatti Clara Hechenberger Hubert Hackl Roman Kessler Michaela Willi Ronald Gstir Anne Krogsdam Alexandra Lusser Werner Poewe Gregor K. Wenning Alexander Hüttenhofer Nadia Stefanova 《PloS one》2016,11(3)
Multiple system atrophy (MSA) is a fatal rapidly progressive α-synucleinopathy, characterized by α-synuclein accumulation in oligodendrocytes. It is accepted that the pathological α-synuclein accumulation in the brain of MSA patients plays a leading role in the disease process, but little is known about the events in the early stages of the disease. In this study we aimed to define potential roles of the miRNA-mRNA regulatory network in the early pre-motor stages of the disease, i.e., downstream of α-synuclein accumulation in oligodendroglia, as assessed in a transgenic mouse model of MSA. We investigated the expression patterns of miRNAs and their mRNA targets in substantia nigra (SN) and striatum, two brain regions that undergo neurodegeneration at a later stage in the MSA model, by microarray and RNA-seq analysis, respectively. Analysis was performed at a time point when α-synuclein accumulation was already present in oligodendrocytes at neuropathological examination, but no neuronal loss nor deficits of motor function had yet occurred. Our data provide a first evidence for the leading role of gene dysregulation associated with deficits in immune and inflammatory responses in the very early, non-symptomatic disease stages of MSA. While dysfunctional homeostasis and oxidative stress were prominent in SN in the early stages of MSA, in striatum differential gene expression in the non-symptomatic phase was linked to oligodendroglial dysfunction, disturbed protein handling, lipid metabolism, transmembrane transport and altered cell death control, respectively. A large number of putative miRNA-mRNAs interaction partners were identified in relation to the control of these processes in the MSA model. Our results support the role of early changes in the miRNA-mRNA regulatory network in the pathogenesis of MSA preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of MSA. 相似文献