全文获取类型
收费全文 | 2252篇 |
免费 | 170篇 |
专业分类
2422篇 |
出版年
2023年 | 7篇 |
2022年 | 24篇 |
2021年 | 30篇 |
2020年 | 28篇 |
2019年 | 50篇 |
2018年 | 51篇 |
2017年 | 48篇 |
2016年 | 82篇 |
2015年 | 121篇 |
2014年 | 121篇 |
2013年 | 154篇 |
2012年 | 195篇 |
2011年 | 169篇 |
2010年 | 103篇 |
2009年 | 103篇 |
2008年 | 142篇 |
2007年 | 141篇 |
2006年 | 120篇 |
2005年 | 116篇 |
2004年 | 109篇 |
2003年 | 96篇 |
2002年 | 90篇 |
2001年 | 32篇 |
2000年 | 17篇 |
1999年 | 17篇 |
1998年 | 23篇 |
1997年 | 28篇 |
1996年 | 21篇 |
1995年 | 22篇 |
1994年 | 21篇 |
1993年 | 23篇 |
1992年 | 18篇 |
1991年 | 14篇 |
1990年 | 14篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 7篇 |
1986年 | 12篇 |
1985年 | 7篇 |
1984年 | 2篇 |
1983年 | 7篇 |
1982年 | 2篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1952年 | 1篇 |
排序方式: 共有2422条查询结果,搜索用时 0 毫秒
31.
Luca Galluzzi Antonella Penna Elena Bertozzini Maria Grazia Giacobbe Magda Vila Esther Garcs Silvia Prioli Mauro Magnani 《Harmful algae》2005,4(6):337
Paralytic shellfish poisoning (PSP) is a syndrome caused by the consumption of shellfish contaminated with neurotoxins produced by organisms of the marine dinoflagellate genus Alexandrium. A. minutum is the most widespread species responsible for PSP in the Western Mediterranean basin. The standard monitoring of shellfish farms for the presence of harmful algae and related toxins usually requires the microscopic examination of phytoplankton populations, bioassays and toxin determination by HPLC. These procedures are time-consuming and require remarkable experience, thus limiting the number of specimens that can be analyzed by a single laboratory unit. Molecular biology techniques may be helpful in the detection of target microorganisms in field samples. In this study, we developed a qualitative PCR assay for the rapid detection of all potentially toxic species belonging to the Alexandrium genus and specifically A. minutum, in contaminated mussels. Alexandrium genus-specific primers were designed to target the 5.8S rDNA region, while an A. minutum species-specific primer was designed to bind in the ITS1 region. The assay was validated using several fixed seawater samples from the Mediterranean basin, which were analyzed using PCR along with standard microscopy procedures. The assay provided a rapid method for monitoring the presence of Alexandrium spp. in mussel tissues, as well as in seawater samples. The results showed that PCR is a valid, rapid alternative procedure for the detection of target phytoplankton species either in seawater or directly in mussels, where microalgae can accumulate. 相似文献
32.
Cametti M Piantanida I Zinić M Dalla Cort A Mandolini L Marjanović M Kralj M 《Journal of inorganic biochemistry》2007,101(8):1129-1132
The Al(III)-salophen complex 1 exhibited strong spectroscopic changes specifically upon addition of polyG and GpG, while double stranded DNA and RNA, and single stranded polyA, polyU and polyC induced negligible spectral changes of 1. Titrations with mono-nucleotides yielded no spectroscopic changes, revealing that there must be at least two consecutive guanines in single stranded oligonucleotide structure for a measurable spectroscopic change of 1. Preliminary results show that 1 has moderate antiproliferative effect on a number of human tumour cell lines. 相似文献
33.
Oddo S Caccamo A Cheng D Jouleh B Torp R LaFerla FM 《Journal of neurochemistry》2007,102(4):1053-1063
The two hallmark pathologies of Alzheimer's disease (AD) are amyloid plaques, composed of the small amyloid-beta (Abeta) peptide, and neurofibrillary tangles, comprised aggregates of the microtubule binding protein, tau. The molecular linkage between these two lesions, however, remains unknown. Based on human and mouse studies, it is clear that the development of Abeta pathology can trigger tau pathology, either directly or indirectly. However, it remains to be established if the interaction between Abeta and tau is bidirectional and whether the modulation of tau will influence Abeta pathology. To address this question, we used the 3xTg-AD mouse model, which is characterized by the age-dependent buildup of both plaques and tangles. Here we show that genetically augmenting tau levels and hyperphosphorylation in the 3xTg-AD mice has no effect on the onset and progression of Abeta pathology. These data suggest that the link between Abeta and tau is predominantly if not exclusively unidirectional, which is consistent with the Abeta cascade hypothesis and may explain why tauopathy-only disorders are devoid of any Abeta pathology. 相似文献
34.
35.
Raschellà G Tanno B Bonetto F Negroni A Claudio PP Baldi A Amendola R Calabretta B Giordano A Paggi MG 《Cell death and differentiation》1998,5(5):401-407
The retinoblastoma family of nuclear factors is composed of RB, the prototype of the tumour suppressor genes and of the strictly related genes p107 and Rb2/p130. The three genes code for proteins, namely pRb, p107 and pRb2/p130, that share similar structures and functions. These proteins are expressed, often simultaneously, in many cell types and are involved in the regulation of proliferation and differentiation. We determined the expression and the phosphorylation of the RB family gene products during the DMSO-induced differentiation of the N1E-115 murine neuroblastoma cells. In this system, pRb2/p130 was strongly up-regulated during mid-late differentiation stages, while, on the contrary, pRb and p107 resulted markedly decreased at late stages. Differentiating N1E-115 cells also showed a progressive decrease in B-myb levels, a proliferation-related protein whose constitutive expression inhibits neuronal differentiation. Transfection of each of the RB family genes in these cells was able, at different degrees, to induce neuronal differentiation, to inhibit [3H]thymidine incorporation and to down-regulate the activity of the B-myb promoter. 相似文献
36.
Magda Vila Maria Grazia Giacobbe Mercedes Mas Ester Gangemi Antonella Penna Nagore Sampedro Filippo Azzaro Jordi Camp Luca Galluzzi 《Harmful algae》2005,4(4):673-695
Alexandrium minutum is a toxic dinoflagellate widespread along the Mediterranean coasts. This species is frequently detected year-round at low concentrations within the Mediterranean basin. However, it only proliferates recurrently in some localities. Two affected areas are the Catalan and Sicilian coasts. In order to identify the factors determining the A. minutum blooms in the Mediterranean Sea, we compare the bloom conditions in two harbours: Arenys de Mar (Catalan coast, Spain) and Syracuse (Sicily, Italy), during 2002–2003. Arenys de Mar harbour is a fishing and leisure harbour and receives an input of freshwater rich in nutrients. Likewise, the Syracuse harbour – located on the Ionian coast of Sicily – is subject to freshwater inputs. Some points of this site are used for productive activities such as shellfish farming. A. minutum from the two areas studied were morphologically and genetically identical. In both sites, recurrent blooms take place from winter to spring. Surface water temperatures and salinities during A. minutum bloom events were 12–14.5 °C and 32–38, and 16–24 °C and 32–37.7 for Arenys and Syracuse, respectively. During the blooms, the spatial distribution of A. minutum in the two harbours, the physicochemical characteristics and the phytoplankton community were studied. Similarities in composition of the phytoplankton community were evidenced, with a clear dominance of dinoflagellates over the other taxa. In Arenys, the second dominant species was Prorocentrum micans followed by Scrippsiella spp. and Dinophysis sacculus. The same species were found in Syracuse although P. triestinum, and alternatively Lingulodinium polyedrum, reached cell densities much higher than the other dinoflagellates giving marked water discolourations. 相似文献
37.
Wangxiao He Pietro Mazzuca Weirong Yuan Kristen Varney Antonella Bugatti Alfredo Cagnotto Cinzia Giagulli Marco Rusnati Stefania Marsico Luisa Diomede Mario Salmona Arnaldo Caruso Wuyuan Lu Francesca Caccuri 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):13-24
Background
HIV-1 matrix protein p17 variants (vp17s) detected in HIV-1-infected patients with non-Hodgkin's lymphoma (HIV-NHL) display, differently from the wild-type protein (refp17), B cell growth-promoting activity. Biophysical analysis revealed that vp17s are destabilized as compared to refp17, motivating us to explore structure-function relationships.Methods
We used: biophysical techniques (circular dichroism (CD), nuclear magnetic resonance (NMR) and thermal/GuHCL denaturation) to study protein conformation and stability; Surface plasmon resonance (SPR) to study interactions; Western blot to investigate signaling pathways; and Colony Formation and Soft Agar assays to study B cell proliferation and clonogenicity.Results
By forcing the formation of a disulfide bridge between Cys residues at positions 57 and 87 we obtained a destabilized p17 capable of promoting B cell proliferation. This finding prompted us to dissect refp17 to identify the functional epitope. A synthetic peptide (F1) spanning from amino acid (aa) 2 to 21 was found to activate Akt and promote B cell proliferation and clonogenicity. Three positively charged aa (Arg15, Lys18 and Arg20) proved critical for sustaining the proliferative activity of both F1 and HIV-NHL-derived vp17s. Lack of any interaction of F1 with the known refp17 receptors suggests an alternate one involved in cell proliferation.Conclusions
The molecular reasons for the proliferative activity of vp17s, compared to refp17, relies on the exposure of a functional epitope capable of activating Akt.General significance
Our findings pave the way for identifying the receptor(s) responsible for B cell proliferation and offer new opportunities to identify novel treatment strategies in combating HIV-related NHL. 相似文献38.
The liver peptide hepcidin regulates body iron, is upregulated in iron overload and inflammation, and is downregulated in iron deficiency/hypoxia. The transmembrane serine protease matriptase-2 (TMPRSS6) inhibits the hepcidin response and its mutational inactivation causes iron-deficient anemia in mice and humans. Here we confirm the inhibitory effect of matriptase-2 on hepcidin promoter; we show that matriptase-2 lacking the serine protease domain, identified in the anemic Mask mouse (matriptase-2(MASK)), is fully inactive and that mutant R774C found in patients with genetic iron deficiency has decreased inhibitory activity. Matriptase-2 cleaves hemojuvelin (HJV), a regulator of hepcidin, on plasma membrane; matriptase-2(MASK) shows no cleavage activity and the human mutant only partial cleavage capacity. Matriptase-2 interacts with HJV through the ectodomain since the interaction is conserved in matriptase-2(MASK). The expression of matriptase-2 mutants in zebrafish results in anemia, confirming the matriptase-2 role in iron metabolism and its interaction with HJV. 相似文献
39.
ABA-regulated promoter activity in stomatal guard cells 总被引:4,自引:0,他引:4
Jane E. Taylor Kirstie F. Renwick Alex A.R. Webb Martin R. McAinsh Antonella Furini Dorothea Bartels Ralph S. Quatrano William R. Marcotte Jr. Alistair M. Hetherington 《The Plant journal : for cell and molecular biology》1995,7(1):129-134
CDeT6-19 is an ABA-regulated gene which has been isolated from Craterostigma plantagineum . The CDeT6-19 gene promoter has been fused to the β- glucuronidase reporter gene ( GUS ) and used to stably transform Arabidopsis thaliana and Nicotiana tabacum . This construct has been shown to be expressed in stomatal guard cells and often in the adjacent epidermal cells of both species in response to both exogenous ABA and drought stress. These results indicate that the stomatal guard cell is competent to relay an ABA signal to the nucleus. In contrast GUS expression directed by the promoter from a predominantly seed-specific, ABA-regulated gene, Em , or the promoter from the ABA-regulated CDeT27-45 gene is not detectable in the epidermal or guard cells of tobacco or Arabidopsis in response to ABA. The fact that not all ABA-regulated gene promoters are active in stomatal guard cells suggests that effective transduction of the signal is dependent upon particular regions within the gene promoter or that guard cells lack all or part of the specific transduction apparatus required to couple the ABA signal to these promoters. This suggests that there are multiple ABA stimulus response coupling pathways. The identification of a regulatory sequence from an ABA-induced gene which is expressed in stomatal guard cells creates the possibility of examining the role of Ca2+ and other second messengers in ABA-induced gene expression. 相似文献