全文获取类型
收费全文 | 1853篇 |
免费 | 118篇 |
国内免费 | 1篇 |
出版年
2023年 | 10篇 |
2022年 | 35篇 |
2021年 | 63篇 |
2020年 | 37篇 |
2019年 | 67篇 |
2018年 | 50篇 |
2017年 | 54篇 |
2016年 | 74篇 |
2015年 | 107篇 |
2014年 | 130篇 |
2013年 | 134篇 |
2012年 | 153篇 |
2011年 | 119篇 |
2010年 | 89篇 |
2009年 | 71篇 |
2008年 | 96篇 |
2007年 | 82篇 |
2006年 | 92篇 |
2005年 | 70篇 |
2004年 | 59篇 |
2003年 | 51篇 |
2002年 | 48篇 |
2001年 | 45篇 |
2000年 | 43篇 |
1999年 | 35篇 |
1998年 | 24篇 |
1997年 | 22篇 |
1996年 | 15篇 |
1995年 | 11篇 |
1994年 | 8篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 15篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1974年 | 4篇 |
1972年 | 2篇 |
1969年 | 1篇 |
1968年 | 2篇 |
排序方式: 共有1972条查询结果,搜索用时 31 毫秒
141.
142.
143.
In primary sensory afferent neurons, Ca2+ plays a vital role in the regulation of cellular processes including receptor and synaptic plasticity, neurotransmitter and trophic factor release and gene regulation. Current understanding of the mechanisms underlying Ca2+ homeostasis of primary sensory afferent neurons is mostly derived from studies on dorsal root ganglia and nodose ganglia neuron cell bodies. Little is known about Ca2+ homeostasis in trigeminal ganglion neurons (TGNs). To determine what cellular processes contribute to electrically-evoked Ca2+ transients in TGNs, we probed Ca2+ regulatory mechanisms in TGN cell bodies from the ophthalmic division with a panel of pharmacological reagents. Ca2+ transients were evoked in fura-2 loaded TGNs by depolarizing the plasma membrane with brief (500 ms) puffs of 50 mM KCl. Cyclopiazonic acid (CPA; 5 microM), an inhibitor of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), significantly decreased the peak amplitude, and slowed the decay, of the KCl-evoked Ca2+ transients in TGNs. The mitochondrial protonophore, carbonyl cyanide 3-chloro-phenylhydrazone (CCCP; 5 microM) significantly increased the peak amplitude of KCl-evoked Ca2+ transients. These data demonstrate that Ca2+ stores do play a major role in Ca2+ homeostasis in TGN cell bodies. To determine the role of the sodium-calcium exchanger (NCX) in KCl-evoked Ca2+ transients in TGNs, we inhibited the exchanger with KB-R7943 (10 microM), or by replacing Na+ with Li+. NCX inhibition did not affect either the peak amplitude or the decay kinetics of the KCl-evoked Ca2+ transients. Therefore, the NCX does not play a significant role in removing cytosolic Ca2+ from TGNs. To test whether the plasma membrane calcium-ATPase (PMCA) contributes to Ca2+ extrusion, we inhibited its activity by a shift to alkaline pH (9.0). At pH 9.0, both the peak amplitude and decay time of the KCl-evoked Ca2+ transient were increased significantly. These data suggest that, in TGNs, the PMCA is the major mechanism for removing cytosolic Ca2+ following electrical activity. 相似文献
144.
Moreira MR Kanashiro A Kabeya LM Polizello AC Azzolini AE Curti C Oliveira CA T-do Amaral A Lucisano-Valim YM 《Life sciences》2007,81(4):317-326
Tissue damage in autoimmune diseases involves excessive production of reactive oxygen species (ROS) triggered by immune complexes (IC) and neutrophil (PMN) interactions via receptors for the Fc portion of IgG (FcgammaR) and complement receptors (CR). Modulation of both the effector potential of these receptors and ROS generation may be relevant to the maintenance of body homeostasis. In the present study, the modulatory effect of four flavonols (myricetin, quercetin, kaempferol, galangin) on rabbit PMN oxidative metabolism, specifically stimulated via FcgammaR, CR or both classes of receptors, was evaluated by luminol- and lucigenin-dependent chemiluminescence assays. Results showed that flavonol inhibitory effect was not dependent on the cell membrane receptor class stimulated but related to the lipophilicity of the compounds (their apparent partition coefficient values were obtained by high-performance liquid chromatography), and was also inversely related to the number of hydroxyl groups in the flavonol B ring and the ROS-scavenger activity (assessed by the luminol--H2O2--horseradish peroxidase reaction). Under the experimental conditions the flavonols tested were not toxic to PMNs (evaluated by lactate dehydrogenase release and trypan blue exclusion) and did not interfere with IC-induced phagocytosis (evaluated by transmission electron microscopy). Our results suggested that inhibition of IC-stimulated PMNs effector functions by the flavonols tested herein was the result of cooperation of different cellular mechanisms. 相似文献
145.
The inner mitochondrial membrane (IMM) is structured in cristae, which contributes to the best functioning of ions and adenylates exchange between the matrix and the intermembrane space. The central hypothesis of this paper is that the cristae structure favours a minimal mean free path of adenylates between translocation sites (translocase/ANT sites) and metabolic sites (ATPase sites). We propose a mathematical model and then give simulations. Based on simple hypotheses about cristae growth, they show that we can account for the major features of the IMM organization and functioning by minimizing the mean interdistance between ADP/ATP translocation and transformation sites. 相似文献
146.
Martinelli CE Sader Milani S Previato JK Figueira M Rangel Montenegro AP Miraki-Moud F Betancourth S Moreira AC Savage MO Camacho-Hübner C 《Hormone research》2007,67(5):224-230
Children with idiopathic short stature (ISS) may have normal or increased growth hormone (GH) responses to provocation tests and achieve a final height (FH) below -2.0 standard deviation score (SDS) if untreated. FH of subjects with high stimulated GH levels has not been studied in detail. AIM: It was the aim of this study to analyse FH in ISS patients with high GH peak responses to the provocation test. PATIENTS AND METHODS: We studied 16 patients (9 pre-pubertal) with ISS and a GH peak >or=40 mU/l to insulin-induced hypoglycaemia. The patients were recalled at age 19.7 +/- 2.5 years for measurement of FH when blood samples were obtained for serum insulin-like growth factor (IGF)-I, IGF binding protein 3, acid-labile subunit and GH binding protein measurements. GH bioactivity was determined using the Nb2 bioassay. RESULTS: FH was -3.1 +/- 1.0 SDS, being significantly lower than target height (TH). At FH, IGF-I levels were within -1.5 and +1.5 SDS for age and sex in 10 patients and higher than +1.5 SDS in 6 patients. IGF binding protein 3, acid-labile subunit, GH binding protein levels and GH bioactivity values were normal. SUMMARY: These data suggest that patients with ISS and high GH levels during a GH stimulation test may have a more compromised FH. The association of severe ISS with a peak GH >40 mU/l might suggest a degree of insensitivity for the GH-IGF-I axis. 相似文献
147.
In this paper it is described for the first time the capability of Myrothecium verrucaria to grow in submerged and solid state cultures using poultry feathers as the only substrate. The fungus produced a protease
with an unusual keratinolytic activity among plant pathogenic fungi. Its crude protease hydrolyzed keratinous substrates at
pH 9.0 and 40 °C in the following order: poultry feather keratin > sheep wool keratin > human nail keratin > human hair keratin.
Protease activity was highly sensitive to phenylmethyl sulphonyl fluoride (PMSF) indicating that the enzyme belonged to the
serine protease family. 相似文献
148.
Juan Carlos Quintero Thelmo Alejandro Lú-Chau Maria Teresa Moreira Gumersindo Feijoo Juan M. Lema 《International biodeterioration & biodegradation》2007,60(4):319-326
In the soil remediation process, the hydrophobic characteristics of pollutants and their affinity for soil matrix may be responsible for mass transfer limitations. The degradation of hexachlorocyclohexane (HCH) isomers present in a spiked soil by the white-rot Bjerkandera adusta was evaluated in a slurry system. Experiments in shaken flasks were performed to evaluate the action of the endogenous microflora, the adsorption of HCH on the fungal biomass and the potential synergic or antagonic actions between the microflora and the fungal biomass. The fungus significantly degraded the HCH isomers from the soil slurry in the following order: α≈γ>δ>β-HCH. The degradation process was further scaled in a 5-l reactor, where the solid load and concentration of the pollutant in the soil were evaluated. At optimal conditions, 100 g soil l−1 and 100 mg total HCH l−1, maximal degradations of 94.5%, 78.5% and 66.1% were attained after 30 d for γ-, α- and δ-HCH isomers, respectively, representing between 1.7 and 3.1-fold the values obtained at small scale. These results indicate that minimising mass transfer resistances is a key factor for HCH degradation from soil. 相似文献
149.
Moreira MF Dos Santos AS Marotta HR Mansur JF Ramos IB Machado EA Souza GH Eberlin MN Kaiser CR Kramer KJ Muthukrishnan S Vasconcellos AM 《Insect biochemistry and molecular biology》2007,37(12):1249-1261
An insoluble white substance was prepared from extracts of eggshells of Aedes aegypti, the yellow fever mosquito and dengue vector. Its infrared and proton NMR spectra were similar to that of standard commercial chitin. This putative chitin-like material, also obtained from ovaries, newly laid and dark eggs, was hydrolyzed in acid and a major product was identified by HPLC to be glucosamine. The eggshell acid hydrolysate was also analyzed by ESI-MS and an ion identical to a glucosamine monoprotonated species was detected. The presence of chitin was also analyzed during different developmental stages of the ovary using a fluorescent microscopy technique and probes specific for chitin. The results showed that a chitin-like material accumulates in oocytes during oogenesis. Streptomyces griseus chitinase pre-treatment of oocytes greatly reduced the chitin-derived fluorescence. Chitinase activity was detected in newborn larvae and eggs prior to hatching. Feeding experiments indicated that the chitin synthesis inhibitor lufenuron inhibited chitin synthesis, either when mosquitoes were allowed to feed directly on lufenuron-treated chickens or when an artificial feeding system was used. Lufenuron inhibited egg hatch, larval development and reduced mosquito viability. These data demonstrate for the first time that (1) a chitin-like material is present in A. aegypti eggs, ovaries and eggshells; (2) a chitin synthesis inhibitor can be used to inhibit mosquito oogenesis; and (3) chitin synthesis inhibitors have potential for controlling mosquito populations. 相似文献
150.
Valente C Moreira R Guedes RC Iley J Jaffar M Douglas KT 《Bioorganic & medicinal chemistry》2007,15(15):5340-5350
A series of 1,4-naphthoquinone derivatives diversely substituted at C-2, C-3, C-5 and C-8, prepared by reaction of amines, amino acids and alcohols with commercial 1,4-naphthoquinones, has been evaluated against papain and bovine spleen cathepsin B. These 1,4-naphthoquinone derivatives were found to be irreversible inhibitors for both cysteine proteases, with second-order rate constants, k(2), ranging from 0.67 to 35.4M(-1)s(-1) for papain, and from 0.54 to 8.03M(-1)s(-1) for cathepsin B. Some derivatives display a hyperbolic dependence of the first-order inactivation rate constant, k(obs), with the inhibitor concentration, indicative of a specific interaction process between enzyme and inhibitor. The chemical reactivity of the compounds towards cysteine as a model thiol is dependent on the naphthoquinone LUMO energy, whereas papain inactivation is not. The 1,4-naphthoquinone derivatives are inactive against the serine protease, porcine pancreatic elastase. 相似文献