全文获取类型
收费全文 | 3250篇 |
免费 | 200篇 |
国内免费 | 3篇 |
专业分类
3453篇 |
出版年
2024年 | 5篇 |
2023年 | 30篇 |
2022年 | 20篇 |
2021年 | 36篇 |
2020年 | 43篇 |
2019年 | 42篇 |
2018年 | 99篇 |
2017年 | 92篇 |
2016年 | 108篇 |
2015年 | 205篇 |
2014年 | 189篇 |
2013年 | 259篇 |
2012年 | 329篇 |
2011年 | 345篇 |
2010年 | 185篇 |
2009年 | 135篇 |
2008年 | 218篇 |
2007年 | 198篇 |
2006年 | 182篇 |
2005年 | 161篇 |
2004年 | 136篇 |
2003年 | 121篇 |
2002年 | 122篇 |
2001年 | 23篇 |
2000年 | 21篇 |
1999年 | 12篇 |
1998年 | 18篇 |
1997年 | 16篇 |
1996年 | 8篇 |
1995年 | 16篇 |
1994年 | 5篇 |
1993年 | 11篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1975年 | 5篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1952年 | 1篇 |
排序方式: 共有3453条查询结果,搜索用时 15 毫秒
1.
J Ignacio Andrés Jesús Alcázar José M Alonso Adolfo Díaz Javier Fernández Pilar Gil Laura Iturrino Encarna Matesanz Theo F Meert Anton Megens Victor K Sipido 《Bioorganic & medicinal chemistry letters》2002,12(2):249-253
Following the programme started at Janssen Research Foundation searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of a series of substituted 2-(Dimethylaminomethyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives. The 5-HT(2A), 5-HT(2C) and H(1) receptor affinities as well as the mCPP antagonistic activity of the compounds synthesised is described. 相似文献
2.
Ethan R. Block Michael A. Tolino Jennifer S. Lozano Kira L. Lathrop Rebecca S. Sullenberger Abigail R. Mazie Jes K. Klarlund 《Molecular biology of the cell》2010,21(13):2172-2181
The ability of epithelia to migrate and cover wounds is essential to maintaining their functions as physical barriers. Wounding induces many cues that may affect the transition to motility, including the immediate mechanical perturbation, release of material from broken cells, new interactions with adjacent extracellular matrix, and breakdown of physical separation of ligands from their receptors. Depending on the exact nature of wounds, some cues may be present only transiently or insignificantly. In many epithelia, activation of the epidermal growth factor receptor (EGFR) is a central event in induction of motility, and we find that its continuous activation is required for progression of healing of wounds in sheets of corneal epithelial cells. Here, we examine the hypothesis that edges, which are universally and continuously present in wounds, are a cue. Using a novel culture model we find that their presence is sufficient to cause activation of the EGFR and increased motility of cells in the absence of other cues. Edges that are bordered by agarose do not induce activation of the EGFR, indicating that activation is not due to loss of any specific type of cell–cell interaction but rather due to loss of physical constraints. 相似文献
3.
Ulrik Pedersen-Bjergaard Lars B geskov Nielsen Kai Jensen Lars Edvinsson Inger Jansen Jes Olesen 《Peptides》1989,10(6):1147-1152
Neurokinin A (NKA), substance P (SP) and the two peptides combined (SP + NKA) were injected intracutaneously on the forearm and into the temporal muscle of healthy volunteers. Pain intensity, cutaneous wheal and flare responses and tenderness of the temporal muscle were quantitated. SP but not NKA induced cutaneous pain. This relates the algesic effect of SP to the specific N-terminal amino acid sequence of the peptide, not shared by NKA. NKA, however, potentiated the algesic effect of SP as SP + NKA induced a significantly prolonged cutaneous pain sensation. Both peptides induced wheals, but only SP induced flare. These results confirm previous studies relating wheal formation to the identical C-terminal amino acid sequence of the two peptides and flare reaction to the N-terminal part of SP. Injections into the temporal muscle did not cause pain or tenderness. 相似文献
4.
Francisco Guillén Angel T. Martinez Maria Jesús Martínez 《Applied microbiology and biotechnology》1990,32(4):465-469
Summary Production of extracellular hydrogen peroxide by fungal oxidases is been investigated as a requirement for lignin degradation. Aryl-alcohol oxidase activity is described in extracellular liquid and mycelium ofPleurotus eryngii and studied under non-limiting nitrogen conditions. This aryl-alcohol oxidase catalyses conversion of primary aromatic alcohols to the corresponding aldehydes and H2O2, showing no activity with aliphatic and secondary aromatic alcohols. The enzyme is stable at pH 4.0–9.0, has maximal activity at 45°–50°C and pH 6.0–6.5, is inhibited by Ag+, Pb2+ and NaN3, and has aK
m
of 1.2 mM using veratryl alcohol as substrate. A single protein band with aryl-alcohol oxidase activity was found in zymograms of extracellular and intracellular crude enzyme preparations fromP. eryngii. 相似文献
5.
Jesús Arellano Filiberto Vázquez Thelma Villegas Georgina Hernández 《Plant cell reports》1996,15(7):455-458
Summary The sesquiterpene quinone currently known as perezone is abundantly produced by the roots of Perezia cuernavacana. This compound is of biotechnological interest since it may be used as a pigment and has several pharmacological properties. In this work we demonstrate that perezone is also produced in transformed root cultures of P. cuernavacana. Hairy roots were induced by inoculation of internodal segments of sterile plants of P. cuernavacana with Agrobacterium rhizogenes AR12 strain. The axenic liquid MS medium cultures of the hairy roots isolated from the internodes showed active growth in the absence of growth regulators. The transformed nature of the tissue was confirmed by genomic integration (PCR and slot blot hybridization) and expression (enzyme activity) of the marker gus-gene. The production of perezone by a transformed root culture was evidenced by IR spectroscopy. Our results offer an alternative for enhanced production of perezone and represent an advantage over its extraction from natural plant populations which present problems in their agronomic culture. 相似文献
6.
Jesús Manuel de la Fuente Amalia Vázquez M. Mar González Miguel Sánchez María Molina César Nombela 《Applied microbiology and biotechnology》1993,38(6):763-769
Thermosensitive mutant strains of Saccharomyces cerevisiae that fail to generate an osmotically stable cell wall when grown at a non-permissive temperature release their cell contents upon expression of the mutation. Therefore, they may represent an alternative for the production of homologous or heterologous protein preparations. In order to analyse the expression of two of these mutations, lyt2 and slt2, we grew the corresponding strains under precisely defined conditions in batch and continuous fermentors. A switch in the temperature of batch cultures from 24° C to 37° C determined lysis of the cells with a significant release of intracellular enzymes. These include alkaline phosphatase and periplasmic proteins such as glucan-degrading enzymes, the pattern of cell lysis and protein release being maintained for about 6 h. One-stage continuous cultures of a lyt2 mutant were maintained for long periods at 37° C; a fraction of the population lysed and released the indicated proteins, but eventually a revertant of the lytic phenotype was selected. To avoid this, a two-stage continuous culture system was developed by connecting two fermentors in series, the effluent from the first one at 24°C being fed to the second one adjusted to 37° C. A steady state of cell lysis and protein liberation was reached in the second-stage fermentor without any evidence of selection of revertants. This system can be very useful for developing conditions for the use of yeast strains to produce protein preparations.
Correspondence to: C. Nombela 相似文献
7.
Enterally administered, heme is a good source of iron in humans and other animals, but the metabolism of heme by enterocytes has not been fully characterized. Caco-2 cells in culture provide a useful model for studying cells that resemble small intestinal epithelium, both morphologically and functionally. In this paper we show that heme oxygenase, the rate-controlling enzyme of heme catabolism, is present in abundance in Caco-2 cells, and that levels of its mRNA and activity can be increased by exposure of the cells to heme or metal ions (cadmium, cobalt). Caco-2 cells also contain biliverdin reductase activity which, in the basal state, is similar to that of heme oxygenase (approximately 40 pmole of product per mg protein per minute); however, when heme oxygenase is induced, biliverdin reductase may become rate-limiting for bilirubin production.Abbreviations BVR
biliverdin reductase
- DMEM
Dulbecco's modified Eagles medium
- DMSO
dimethyl sulfoxide
- HO
heme oxygenase
- 1xSSC
a solution of 0.015 M sodium citrate/0.15 sodium chloride 相似文献
8.
Edgar Antonio Rodríguez-Negrete Enrique Alejandro Guevara-Rivera Ángela Paulina Arce-Leal Norma Elena Leyva-López Jesús Méndez-Lozano 《Molecular Plant Pathology》2023,24(10):1300-1311
The nonstructural protein NSm of tomato spotted wilt virus (TSWV) has been identified as the avirulence determinant of the tomato single dominant Sw-5 resistance gene. Although Sw-5 effectiveness has been shown for most TSWV isolates, the emergence of resistance-breaking (RB) isolates has been observed. It is strongly associated with two point mutations (C118Y or T120N) in the NSm viral protein. TSWV-like symptoms were observed in tomato crop cultivars (+Sw-5) in the Baja California peninsula, Mexico, and molecular methods confirmed the presence of TSWV. Sequence analysis of the NSm 118–120 motif and three-dimensional protein modelling exhibited a noncanonical C118F substitution in seven isolates, suggesting that this substitution could emulate the C118Y-related RB phenotype. Furthermore, phylogenetic and molecular analysis of the full-length genome (TSWV-MX) revealed its reassortment-related evolution and confirmed that putative RB-related features are restricted to the NSm protein. Biological and mutational NSm 118 residue assays in tomato (+Sw-5) confirmed the RB nature of TSWV-MX isolate, and the F118 residue plays a critical role in the RB phenotype. The discovery of a novel TSWV-RB Mexican isolate with the presence of C118F substitution highlights a not previously described viral adaptation in the genus Orthotospovirus, and hence, the necessity of further crop monitoring to alert the establishment of novel RB isolates in cultivated tomatoes. 相似文献
9.
Diana Villegas-Coronado Jesús Adriana Soto-Guzman Juan Manuel Martínez-Soto Nayelli Guadalupe Teran-Saavedra Ana Maria Guzman-Partida Luz Vazquez-Moreno Ana Gloria Villalba-Villalba Amir Maldonado Irlanda Lagarda-Diaz 《化学与生物多样性》2023,20(7):e202300051
Acute monocytic leukemia is a type of myeloid leukemia that develops in monocytes. The current clinical therapies for leukemia are unsatisfactory due to their side effects and nonspecificity toward target cells. Some lectins display antitumor activity and may specifically recognize cancer cells by binding to carbohydrate structures on their surface. Therefore, this study evaluated the response of the human monocytic leukemia cell lines THP-1 to the Olneya tesota PF2 lectin. The induction of apoptosis and reactive oxygen species production in PF2-treated cells was evaluated by flow cytometry, and the lectin-THP-1 cell interaction and mitochondrial membrane potential were evaluated by confocal fluorescence microscopy. PF2 genotoxicity was evaluated by DNA fragmentation analysis via gel electrophoresis. The results showed that PF2 binds to THP-1 cells, triggers apoptosis and DNA degradation, changes the mitochondrial membrane potential, and increases reactive oxygen species levels in PF2-treated THP-1 cells. These results suggest the potential use of PF2 for developing alternative anticancer treatments with enhanced specificity. 相似文献
10.
José de JesÚs Garcia M. Tuena de Gómez-Puyou A. Gómez-Puyou 《Journal of bioenergetics and biomembranes》1995,27(1):127-136
The effect of trifluoperazine (TFP) on the ATPase activity of soluble and paniculate F1ATPase and on ATP synthesis driven by succinate oxidation in submitochondrial particles from bovine heart was studied at pH 7.4 and 8.8. At the two pH. TFP inhibited ATP hydrolysis. Inorganic phosphate protected against the inhibiting action of TFP. The results on the effect of various concentrations of phosphate in the reversal of the action of TFP on hydrolysis at pH 7.4 and 8.8 showed that H2PO
4
–
is the species that competes with TFP. The effect of TFP on oxidative phosphorylation was studied at concentrations that do not produce uncoupling or affect the aerobic oxidation of succinate (<15M). TFP inhibited oxidative phosphorylation to a higher extent at pH 8.8 than at pH 7.4; this was through a diminution in theV
max, and an increase in theK
m for phosphate. Data on phosphate uptake during oxidative phosphorylation at several pH showed that H2PO
4
–
is the true substrate for oxidative phosphorylation. Thus, in both synthesis and hydrolysis of ATP, TFP and H2PO
4
–
interact with a common site. However, there is a difference in the sensitivity to TFP of ATP synthesis and hydrolysis; this is more noticeable at pH 8.8, i.e. ATPase activity of soluble F1 remains at about 40% of the activity of the control in a concentration range of TFP of 40–100M, whereas in oxidative phosphorylation 14M TFP produces a 60% inhibition of phosphate uptake. 相似文献