全文获取类型
收费全文 | 15138篇 |
免费 | 1030篇 |
国内免费 | 1篇 |
出版年
2023年 | 107篇 |
2022年 | 203篇 |
2021年 | 445篇 |
2020年 | 293篇 |
2019年 | 356篇 |
2018年 | 448篇 |
2017年 | 409篇 |
2016年 | 633篇 |
2015年 | 955篇 |
2014年 | 1015篇 |
2013年 | 1259篇 |
2012年 | 1488篇 |
2011年 | 1336篇 |
2010年 | 834篇 |
2009年 | 713篇 |
2008年 | 874篇 |
2007年 | 855篇 |
2006年 | 805篇 |
2005年 | 661篇 |
2004年 | 624篇 |
2003年 | 548篇 |
2002年 | 442篇 |
2001年 | 93篇 |
2000年 | 68篇 |
1999年 | 99篇 |
1998年 | 84篇 |
1997年 | 74篇 |
1996年 | 64篇 |
1995年 | 48篇 |
1994年 | 54篇 |
1993年 | 37篇 |
1992年 | 32篇 |
1991年 | 23篇 |
1990年 | 22篇 |
1989年 | 20篇 |
1988年 | 12篇 |
1987年 | 18篇 |
1986年 | 8篇 |
1985年 | 10篇 |
1984年 | 15篇 |
1983年 | 14篇 |
1982年 | 5篇 |
1981年 | 9篇 |
1980年 | 10篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 7篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1972年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 515 毫秒
971.
Fernanda A. H. Batista Leandro S. Goto Wanius Garcia Derminda I. de Moraes Mario de Oliveira Neto Igor Polikarpov Marcia R. Cominetti Heloísa S. Selistre-de-Araújo Leila M. Beltramini Ana Paula Ulian Araújo 《European biophysics journal : EBJ》2010,39(8):1193-1205
Lectins have been classified into a structurally diverse group of proteins that bind carbohydrates and glycoconjugates with
high specificity. They are extremely useful molecules in the characterization of saccharides, as drug delivery mediators,
and even as cellular surface makers. In this study, we present camptosemin, a new lectin from Camptosema ellipticum. It was characterized as an N-acetyl-d-galactosamine-binding homo-tetrameric lectin, with a molecular weight around 26 kDa/monomers. The monomers were stable over
a wide range of pH values and exhibited pH-dependent oligomerization. Camptosemin promoted adhesion of breast cancer cells
and hemagglutination, and both activities were inhibited by its binding of sugar. The stability and unfolding/folding behavior
of this lectin was characterized using fluorescence and far-UV circular dichroism spectroscopies. The results indicate that
chemical unfolding of camptosemin proceeds as a two-state monomer-tetramer process. In addition, small-angle X-ray scattering
shows that camptosemin behaves as a soluble and stable homo-tetramer molecule in solution. 相似文献
972.
Júlia D. Moreira Luisa Knorr Marcelo Ganzella Ana Paula Thomazi Carolina G. de Souza Débora G. de Souza Carolina F. Pitta Tadeu Mello e Souza Susana Wofchuk Elaine Elisabetsky Lúcia Vinadé Marcos L.S. Perry Diogo O. Souza 《Neurochemistry international》2010,56(6-7):753-759
Essential omega-3 polyunsaturated fatty acids (ω3) are crucial to brain development and function, being relevant for behavioral performance. In the present study we examined the influence of dietary ω3 in the development of the glutamatergic system and on behavior parameters in rats. Female rats received isocaloric diets, either with ω3 (ω3 group) or a ω3 deficient diet (D group). In ontogeny experiments of their litters, hippocampal immunocontent of ionotropic NMDA and AMPA glutamatergic receptors subunits (NR2 A\B and GluR1, respectively) and the alpha isoform of the calcium-calmodulin protein kinase type II (αCaMKII) were evaluated. Additionally, hippocampal [3H]glutamate binding and uptake were assessed. Behavioral performance was evaluated when the litters were adult (60 days old), through the open-field, plus-maze, inhibitory avoidance and flinch-jump tasks. The D group showed decreased immunocontent of all proteins analyzed at 02 days of life (P2) in comparison with the ω3 group, although the difference disappeared at 21 days of life (except for αCaMKII, which content normalized at 60 days old). The same pattern was found for [3H]glutamate binding, whereas [3H]glutamate uptake was not affected. The D group also showed memory deficits in the inhibitory avoidance, increased in the exploratory pattern in open-field, and anxiety-like behavior in plus-maze. Taken together, our results suggest that dietary ω3 content is relevant for glutamatergic system development and for behavioral performance in adulthood. The putative correlation among the neurochemical and behavioral alterations caused by dietary ω3 deficiency is discussed. 相似文献
973.
Moreschi E Hernandes L Dantas JA da Silva MA Casaroto AR Bersani-Amado CA 《Histology and histopathology》2010,25(12):1547-1556
The aim of the present study was to evaluate histologically and radiographically the tissue response to dolomite [CaMg(CO3)2] and its osteogenic potential in the repair of bone cavities in the calvaria of rats. A bone defect 10 mm in diameter and 1 mm deep was made in the calvaria of male Wistar rats. The defects were filled with dolomite, inorganic bovine bone (positive control), or coagulum (negative control). The animals were euthanized 7, 15, 30, and 60 days after surgery, and specimens were collected for radiographic and microscopic analyses. The bone defects were processed for paraffin embedding and H&E staining. The histological study revealed that dolomite stimulated a moderate inflammatory response, with programmed cell death in the first 15 days, compared to bovine bone which showed a moderate to intense acute response. In the chronic phase, the inflammatory response was characterized by the occurrence of macrophages organized as epithelioid cells in the dolomite group, and giant cells in the bovine-bone group. Fibrosis developed in all three groups; however, encapsulation of the fragments, reabsorption, and osteoconductive activity occurred only in the defects filled with bovine bone. The radiographic analysis showed that the bovine bone was most efficient in the repair of the defects, followed by the dolomite and the coagulum. This study demonstrated that the dolomite stimulated a moderate acute inflammatory response with programmed cell death, and a chronic inflammatory response by means of the phagocytic mononuclear system. Although osteo-conductive activity was not shown, the dolomite favored the repair process, compared to the coagulum group. 相似文献
974.
Joo‐Yong Lee Waixing Tang Esther Wong Ya‐Sheng Gao Udai B Pandey Susmita Kaushik Emily Tresse Jianrong Lu J Paul Taylor Ana Maria Cuervo Tso‐Pang Yao 《The EMBO journal》2010,29(5):969-980
Autophagy is primarily considered a non‐selective degradation process induced by starvation. Nutrient‐independent basal autophagy, in contrast, imposes intracellular QC by selective disposal of aberrant protein aggregates and damaged organelles, a process critical for suppressing neurodegenerative diseases. The molecular mechanism that distinguishes these two fundamental autophagic responses, however, remains mysterious. Here, we identify the ubiquitin‐binding deacetylase, histone deacetylase‐6 (HDAC6), as a central component of basal autophagy that targets protein aggregates and damaged mitochondria. Surprisingly, HDAC6 is not required for autophagy activation; rather, it controls the fusion of autophagosomes to lysosomes. HDAC6 promotes autophagy by recruiting a cortactin‐dependent, actin‐remodelling machinery, which in turn assembles an F‐actin network that stimulates autophagosome–lysosome fusion and substrate degradation. Indeed, HDAC6 deficiency leads to autophagosome maturation failure, protein aggregate build‐up, and neurodegeneration. Remarkably, HDAC6 and F‐actin assembly are completely dispensable for starvation‐induced autophagy, uncovering the fundamental difference of these autophagic modes. Our study identifies HDAC6 and the actin cytoskeleton as critical components that define QC autophagy and uncovers a novel regulation of autophagy at the level of autophagosome–lysosome fusion. 相似文献
975.
Jelena Djordjevic Ana Djordjevic Miroslav Adzic Marija B. Radojcic 《Cellular and molecular neurobiology》2010,30(5):693-700
Chronic neuroendocrine stress usually leads to the elevation of the stress hormones and increased metabolic rate, which is
frequently accompanied by oxidative damage to the CNS. In the present study we hypothesized that chronic psychosocial isolation
(CPSI) of male Wistar rats, characterized by decreased serum corticosterone (CORT), unaltered catecholamines (CTs), and low
blood glucose (GLU), may also promote oxidative imbalance in the CNS, by targeting antioxidant defense system. To test it,
we have examined the relation between these input signals and protein expression/activity of antioxidant enzymes (AOEs): superoxide
dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GLR) in the hippocampus (HIPPO)
of CPSI animals. We found that CPSI did not affect SODs or CAT, but decreased activity of GPx and compromised GLR, an enzyme
highly dependent on blood GLU for its substrate precursor. Further, we have tested whether the CPSI experience altered AOEs
response to a novelty stress, and found that it attenuated peroxide-metabolizing enzymes, CAT and GPx, and decreased GLR activity,
even though blood GLU was restored. The altered ratios of hippocampal AOEs in CPSI animals, which were worsened under the
combined stress conditions, may lead to the accumulation of peroxide products and oxidative imbalance. The mechanism by which
CPSI generate oxidative imbalance in the HIPPO is most likely based on poor systemic energy conditions set by this stress.
Such conditions may cause functional decline of CNS structures, such as HIPPO, and are likely to promote state linked to onset
of many mood disorders. 相似文献
976.
977.
Bárbara Santos Pires da Silva Eloísa Bonfá Júlio César Bertacini de Moraes Carla Gonçalves Schain Saad Ana Cristina de Medeiros Ribeiro Célio Roberto Gonçalves Jozélio Freire de Carvalho 《Biologicals》2010,38(5):567-569
The objective of this study was to evaluate the influence of anti-tumor necrosis factor (anti-TNF) in juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Sixty-two patients were investigated: 7 JIA; 37 AS; and 18 PsA. Caucasian race accounted for 79% and 29% were female. Mean age was 40.4 ± 12.6years. None of the patients had a history of diabetes, and none had used oral hypoglycemic agents or insulin. Treatment was with adalimumab, infliximab and etanercept. Glucose, inflammatory markers and prednisone dose were assessed at baseline, as well as after three and six months of treatment. The mean erythrocyte sedimentation rate was significantly lower at three months and six months than at baseline (13.7 ± 18.0 and 18 ± 22.5 vs. 27.9 ± 23.4 mm; p = 0.001). At baseline, three months and six months, we found the following: mean C-reactive protein levels were comparable (22.1 ± 22.7, 14.5 ± 30.7 and 16.0 ± 23.8 mg/L, respectively; p = 0.26); mean glucose levels remained unchanged (90.8 ± 22.2 mg/dl, 89.5 ± 14.6 mg/dl and 89.8 ± 13.6 mg/dl, respectively; p = 0.91); and mean prednisone doses were low and stable (3.9 ± 4.9 mg/day, 3.7 ± 4.8 mg/day and 2.6 ± 4.0 mg/day, respectively; p = 0.23). During the first six months of treatment, anti-TNF therapy does not seem to influence glucose metabolism in JIA, AS or PsA. 相似文献
978.
Given the demand for improved methods for detecting and characterizing RNA variants in situ, we developed a quantitative method for detecting RNA alternative splicing variants that combines in situ hybridization of fluorescently labeled peptide nucleic acid (PNA) probes with confocal microscopy Förster resonance energy transfer (FRET). The use of PNA probes complementary to sequences flanking a given splice junction allows to specifically quantify, within the cell, the RNA isoform generating such splice junction as FRET efficiency measure. The FRET-based PNA fluorescence in situ hybridization (FP-FISH) method offers a conceptually new approach for characterizing at the subcellular level not only splice variant isoform structure, location, and dynamics but also potentially a wide variety of close range RNA–RNA interactions. In this paper, we explain the FP-FISH technique workflow for reliable and reproducible results. 相似文献
979.
Ana Paula Chiaverini Pinto Alessandra Cristina B. A. Monteiro-Hara Liliane Cristina Liborio Stipp Beatriz Madalena Januzzi Mendes 《In vitro cellular & developmental biology. Plant》2010,46(1):28-33
Passiflora alata in vitro organogenesis was studied based on explant type, culture medium composition, and incubation conditions. The results indicated
that the morphogenic process occurred more efficiently when hypocotyl segment-derived explants were cultured in media supplemented
with cytokinin and AgNO3 incubated under a 16-h photoperiod. The shoot bud elongation and plant development were obtained by transferring the material
to MSM culture medium supplemented with GA3 and incubated in flasks with vented lids. Histological analyses of the process revealed that the difficulties in obtaining
plants could be related to the development of protuberances and leaf primordia structures, which did not contain shoot apical
meristem. Roots developed easily by transferring elongated shoots to 1/2 MSM culture medium. Plant acclimatization occurred
successfully, and somaclonal variation was not visually detected. The efficiency of this organogenesis protocol will be evaluated
for genetic transformation of this species to obtain transgenic plants expressing genes that can influence the resistance
to Cowpea aphid borne mosaic virus. 相似文献
980.
The impact of cold-water immersion on power production in the vertical jump and the benefits of a dynamic exercise warm-up 总被引:1,自引:0,他引:1
Dixon PG Kraemer WJ Volek JS Howard RL Gomez AL Comstock BA Dunn-Lewis C Fragala MS Hooper DR Häkkinen K Maresh CM 《Journal of strength and conditioning research / National Strength & Conditioning Association》2010,24(12):3313-3317
The purpose of this study was to examine the influence of a cold treatment and a dynamic warm-up on lower body power in the form of a countermovement vertical jump (CMVJ). Nine physically active men, who were either current or ex-National Collegiate Athletic Association (NCAA) Division 1 athletes, consented to participate in the study. Using a balanced, randomized presentation and a within-subject design, each subject performed 4 environmental and warm-up protocols (i.e., ambient temperature without warm-up, ambient temperature with warm-up, cold without warm-up, or cold with warm-up). Two sets of 3 maximal effort CMVJs were performed on a force plate at each testing time point. For each protocol, the subjects completed a pretest set of CMVJ (pretreatment [PRE]), were then exposed to 1 of the 2 temperature treatments, completed another set of CMVJ (initial [IT]), then either went through a 15-minute warm-up, or were asked to sit in place. Then a final set of CMVJs was completed (posttreatment [PT]). The primary finding in this study was that warm-up was effective in offsetting the negative effects of cold exposure on CMVJ power. There was a significant main effect for Time (PRE > PT > IT), and there was a significant (p ≤ 0.05) main effect for Trial (AMB = AMBWU > COLDWU > COLD). Because athletic competitions happen in various colder climates, it is important to make sure that a proper warm-up be completed to maximize the athlete's power output. The results of this study demonstrate that when athletes are exposed to cold conditions, it is recommended that before practice or play, a dynamic warm-up be employed to optimize performance. 相似文献