全文获取类型
收费全文 | 2462篇 |
免费 | 136篇 |
国内免费 | 1篇 |
出版年
2023年 | 5篇 |
2022年 | 28篇 |
2021年 | 44篇 |
2020年 | 28篇 |
2019年 | 48篇 |
2018年 | 55篇 |
2017年 | 34篇 |
2016年 | 63篇 |
2015年 | 116篇 |
2014年 | 112篇 |
2013年 | 197篇 |
2012年 | 165篇 |
2011年 | 174篇 |
2010年 | 114篇 |
2009年 | 113篇 |
2008年 | 145篇 |
2007年 | 161篇 |
2006年 | 135篇 |
2005年 | 110篇 |
2004年 | 105篇 |
2003年 | 103篇 |
2002年 | 96篇 |
2001年 | 23篇 |
2000年 | 21篇 |
1999年 | 30篇 |
1998年 | 22篇 |
1997年 | 27篇 |
1996年 | 24篇 |
1995年 | 19篇 |
1994年 | 12篇 |
1993年 | 25篇 |
1992年 | 15篇 |
1991年 | 18篇 |
1990年 | 17篇 |
1989年 | 12篇 |
1988年 | 18篇 |
1987年 | 14篇 |
1986年 | 5篇 |
1985年 | 10篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 9篇 |
1981年 | 13篇 |
1980年 | 11篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1972年 | 6篇 |
1969年 | 7篇 |
排序方式: 共有2599条查询结果,搜索用时 218 毫秒
941.
Glycosylation consists in the covalent linkage of a carbohydrate structure to membrane bound and secreted glycoconjugates. It is a common post-translational modification that serves multiple functions in cell differentiation, signaling and intercellular communication. Unlike DNA/RNA/protein, the addition of complex carbohydrates is not-template driven and it is conceivable that both genetics and environmental factors might interact to influence glycosylation machinery in several pathological processes. Over the last few decades, the recognition of Congenital Disorders of Glycosylation (CDG) as an increasing number of genetic diseases of glycosylation with almost constant nervous system involvement, dramatically illustrated the consequences of abnormal glycosylation as improper CNS development and function. In addition, CDG recognition contributed to postulate that aberrant glycosylation processes might play a role in multifactorial, complex CNS diseases. On this context, CNS glycomics explores the effects of possible aberrant glycosylation to identify potential glyco-biomarkers useful for the diagnosis and ultimately for potential intervention strategies in neurological diseases. Up to date, CNS glycomics is an emerging, still uncharted area because of the specificity of CNS glycosylation, the complexity of the neurological disorders and for the inaccessibility and invasiveness of disease relevant samples. Here we review current knowledge on clinical glycomics of nervous system diseases, starting with CDG to include those pediatric and adulthood neuropsychiatric diseases where some evidences suggest that multifactor determinants converge to dysregulate glycosylation. Conventional and mass spectrometry-based high throughput technology for glyco-biomarker detection in CNS diseases is reported. 相似文献
942.
The characteristic surface lipid compositions of several C3 and C4 plants are discussed. C4 plants produce surface lipids (epicuticular waxes) made up of the ubiquitous classes of aliphatic compounds: free fatty acids, aldehydes, primary alcohols, alkanes and aliphatic linear esters. C3 plants synthesize surface lipids comprising the ubiquitous classes and either of the two following groups of compound: (i) lβ-diketones, hydroxy lβ-diketones, alkan-2-ol esters; (il) ketones and secondary alcohols with the functional group in the middle of the hydrocarbon chain. These features are suggested to represent physioIogical characteristics of the plant and to be related to ecological adaptations. Wax class compositions might also be an ancillary method for defining the C3 or C4 mechanism of CO2 assimilation in cases where uncertainty exists. 相似文献
943.
Angela Alama Raffaella Meazza Federica Barbieri Roberto Biassoni Mauro Mazzei Angelo Nicolin 《Experimental cell research》1993,206(2)
Antisense oligonucleotides appear to offer considerable promise as sequence-specific inhibitors of gene expression. Different cellular targets for oligodeoxynucleotides with oncologic interest have been identified such as oncogenes, growth factors, and cell cycle-related genes. DNA polymerase α (polα) plays a relevant role in DNA synthesis and cell proliferation. Polα gene expression is constitutive throughout the cell cycle and its mRNA content and activity are related to the growth rate and neoplastic phenotype. The effects of a 18-mer polα antisense oligomer on the proliferation of the MDA-MB 231 breast cancer cell line have been investigated. After 48 h in culture with oligomers (10 μM), about 50% growth inhibition was observed in antisense-treated cells, as evaluated by 3-(4, 5-dimethythiazol-2yl)-2, 5-diphenyltetrazolium bromide assay and cell count. [3H]Thymidine incorporation exhibited a 90% inhibition of DNA synthesis associated to 64% accumulation of cells at the G1-S border of the cycle as by flow cytometry, at 24 h. Northern hybridization and SDS-PAGE of immunoprecipitated MDA-MB 231 cell lysates revealed a decreased expression of polα mRNA and a reduction of the 180-kDa polypeptide, respectively. Collectively, the data further confirm the relevance of polα in the replicative cycle, as well as strengthen the potentiality of the antisense strategy for the control of gene expression and cell growth. 相似文献
944.
Luigi Barbieri Letizia Polito Andrea Bolognesi Marialibera Ciani Emanuele Pelosi Valentina Farini Ajay K. Jha Neelam Sharma Jorge M. Vivanco Angela Chambery Augusto Parente Fiorenzo Stirpe 《Biochimica et Biophysica Acta (BBA)/General Subjects》2006
The basic protein fraction of tissue extracts from 40 edible plants inhibited cell-free protein synthesis and released adenine from herring sperm DNA, thus having adenine glycosylase activity. This suggested the presence of ribosome-inactivating proteins (RIPs) in the plant extracts. This indication was further strengthened by the presence of the two activities after a partial chromatographic purification of three extracts, including that from Lycopersicon esculentum (tomato), which had very low activity. From the extract of Cucurbita moschata (pumpkin), the most active one, a glycoprotein of 30,665 Da was purified which had the properties of a RIP, in that (i) it inhibited protein synthesis by a rabbit reticulocyte lysate with IC50 (concentration giving 50% inhibition) 0.035 nM (1.08 ng ml−1) and by HeLa, HT29 and JM cells with IC50 in the 100 nM range, (ii) deadenylated hsDNA and other polynucleotidic substrates, and (iii) depurinated yeast rRNA at a concentration of 0.1 ng ml−1, all values being comparable to those of other RIPs. The C. moschata RIP gave a weak cross-reaction only with an antiserum against dianthin 32, but not with antisera against other RIPs, and had superoxide dismutase, antifungal and antibacterial activities. 相似文献
945.
946.
Mangieri D Nico B Benagiano V De Giorgis M Vacca A Ribatti D 《Journal of cellular and molecular medicine》2008,12(3):1023-1028
947.
Renio S. Mendes Luiz R. Evangelista Sidinei M. Thomaz Angelo A. Agostinho Luiz C. Gomes 《Ecography》2008,31(4):450-456
Several indices have been created to measure diversity, and the most frequently used are the Shannon-Wiener (H) and Simpson (D) indices along with the number of species (S) and evenness (E). Controversies about which index should be used are common in literature. However, a generalized entropy (Tsallis entropy) has the potential to solve part of these problems. Here we explore a family of diversity indices (Sq ; where q is the Tsallis index) and evenness (Eq ), based on Tsallis entropy that incorporates the most used indices. It approaches S when q=0, H when q→1 and gives D when q=2. In general, varying the value of the Tsallis index (q), Sq varies from emphasis on species richness (q<1) to emphasis on dominance (q>1). Similarly, Eq also works as a tool to investigate diversity. In particular, for a given community, its minimum value represents the maximum deviation from homogeneity (Eq =1) for a particular q (herein named q*). It is remarkable that our analysis indicates that q* and its corresponding evenness, Eq* , are negatively affected by S when using simulated data. They may represent an index related to species rarity. Furthermore, Sq* (i.e. the value of Sq for a specific q*) is positively affected by richness that is an important property of any diversity index. In general, our findings indicate that the indices H, D, S, Sq* , E and Eq* are only part of a whole set of possibilities. In addition, the ecological properties of Eq* and Sq* , proposed here for the first time, show promise in ecology. 相似文献
948.
Multiple sequence alignments are successfully applied in many studies for under- standing the structural and functional relations among single nucleic acids and pro- tein sequences as well as whole families. Because of the rapid growth of sequence databases, multiple sequence alignments can often be very large and difficult to visualize and analyze. We offer a new service aimed to visualize and analyze the multiple alignments obtained with different external algorithms, with new features useful for the comparison of the aligned sequences as well as for the creation of a final image of the alignment. The service is named FASMA and is available at http: //bioinformatica.isa.cnr.it /FASMA /. 相似文献
949.
An efficient method for producing alpha(1,3)-galactosyltransferase gene knockout pigs 总被引:5,自引:0,他引:5
Harrison S Boquest A Grupen C Faast R Guildolin A Giannakis C Crocker L McIlfatrick S Ashman R Wengle J Lyons I Tolstoshev P Cowan P Robins A O'Connell P D'Apice AJ Nottle M 《Cloning and stem cells》2004,6(4):327-331
We have reported relatively efficient methods for somatic cell nuclear transfer and for knocking out the alpha(1,3)-galactosyltransferase (alpha1,3-GT) gene in porcine fetal fibroblasts using a nonisogenic promoterless construct approach. Here we report the production of alpha1,3-GT gene knockout pigs using these procedures. Seven alpha1,3-GT gene knockout cell clones were identified by long-range PCR from 108 neomycin resistant (neo(R)) colonies, giving a 6.5% targeting efficiency. Three cell clones were used for nuclear transfer. Nuclear transfer was performed using a fusion before activation protocol using in vitro-matured adult oocytes. Between 51 and 110 fused couplets were transferred to 10 recipients synchronized 1 day behind the embryos. Parturition was induced on day 115, and piglets were delivered by caesarean section. Four recipients gave birth to a total of 18 live piglets. All pigs were female, and all three clones resulted in the birth of live pigs. alpha1,3-GT gene knockout pigs were identified by long-range PCR and confirmed by Southern blot analysis. The efficiency (embryos transferred/piglets born) of our cloning protocol was 1.9% for all transfers and 4.6% for animals that gave birth. 相似文献
950.
Angelo Benedetti Alessandro F. Casini Marco Ferrali Mario Comporti 《Chemico-biological interactions》1977,17(2):167-183
The distribution of carbon tetrachloride-induced alterations of membrane lipids in various fractions of liver microsomal lipids was studied. The chromatographic spot (referred to as the “D” spot in the previous paper [1]) which has been shown to contain the compounds responsible for the diene conjugation absorption [1], was found in the fatty acid methyl esters prepared from the fraction containing phosphatidylethanolamine (PE) and also in those obtained from the fraction containing phosphatidylserine (PS) and phosphatidylinositol (PI). The absorption of conjugated dienes was very marked in PE and less intense in PS and PI. The fatty acid methyl esters prepared from the fraction containing phosphatidylcholine (PC) showed no presence of the “D” spot and minimal absorption of conjugated dienes.A decrease in arachidonic acid content was found in the fraction containing PE, while no change in content of this fatty acid was found in the fraction containing PC. Results similar to those observed for PC were also found for neutral lipids (NL).Analysis of the fatty acid methyl esters of the various lipid fractions by gas-liquid chromatography (GLC) with an electron capture detector (ECD) gave a qualitative index of the free radical attack by CCl4 metabolites. Quantitative estimation was attained by study of the irreversible binding of 14C from 14CCl4 to the various lipid fractions. It was found that the fraction containing PS had the highest specific activity, while the fraction containing PC had the lowest specific activity of all the phospholipids. Thin layer chromatography (TLC) of the fraction containing PS revealed that only 11% of the radioactivity was associated with the pure PS moiety, while the remainder was associated with uncharacterized lipids (probably oxidation products).The possible relevance of the alterations induced by carbon tetrachloride in the various phospholipid fractions of liver microsomes to functional changes is discussed. 相似文献