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131.
Sotelo E Fraiz N Yáñez M Terrades V Laguna R Cano E Raviña E 《Bioorganic & medicinal chemistry》2002,10(9):2873-2882
A series of 6-phenyl-3(2H)-pyridazinones with a diverse range of substituents in the 5-position have been prepared and evaluated in the search for new antiplatelet agents. A significant dependence of the substituent on the inhibitory effect has been observed. The pharmacological study of these compounds confirms that modification of the chemical group at position 5 of the 6-phenyl-3(2H)-pyridazinone system influences both variations in the antiplatelet activity and the mechanism of action. 相似文献
132.
Jagerovic N Cano C Elguero J Goya P Callado LF Meana JJ Girón R Abalo R Ruiz D Goicoechea C Martín MA 《Bioorganic & medicinal chemistry》2002,10(3):817-827
The synthesis of new fentanyl analogues in which the benzene ring of the propioanilido group has been replaced by phenylpyrazole is described. Antinociceptive activity was evaluated using the writhing and hot plate tests in mice. Two compounds, and, showed interesting analgesic properties, being more potent than morphine and less than fentanyl but with longer duration of action. These compounds inhibited the electrically evoked muscle contraction of guinea pig ileum and mouse vas deferens but not that of rabbit vas deferens and the effects could be reversed by antagonists (naloxone and/or CTOP), thus indicating that the compounds acted as mu agonists. Finally, the binding data confirmed that the compounds had high affinity and selectivity for the mu receptor. 相似文献
133.
Ana Martínez-Pe?alver Nuria Pedrol Manuel J. Reigosa Adela M. Sánchez-Moreiras 《Journal of Plant Growth Regulation》2012,31(3):406-415
We investigated the effects of the secondary metabolite protocatechualdehyde (PCA, 3,4-dihydroxybenzaldehyde) on stress markers, including fluorescence parameters and the concentrations of pigments, free radicals, protein, and lipid peroxides, in adult plants of Arabidopsis thaliana. The content of proline, carotenoids, and chlorophylls a and b peaked 9?h after administration of 3?mM PCA (the highest concentration used in this study), although malonyldialdehyde and dry mass contents peaked 24?h following PCA treatment. Leaf staining revealed peak production of O2 ? between 30 and 90?min post-treatment and peak production of H2O2 between 1 and 9?h post-treatment. Several effects, including the observed furling of leaf margins (leaf rolling), the increases in proline content and dry to fresh weight ratio, and the oxidative burst, are reminiscent of the plant response to drought. Early dehydration in PCA-treated plants was confirmed by decreases in leaf water potential, relative water content, and stomatal opening in the first hours of treatment. Thus, PCA seems to be either inducing water deficiency stress (probably through action in the roots) or directly triggering antidrought defenses. In either case, plants showed tolerance to the concentrations employed in this study, with most of the parameters observed having recovered control values within a week of treatment. 相似文献
134.
Martinez-Navio JM Climent N Gallart T Lluis C Franco R 《Immunology and cell biology》2012,90(6):594-600
After nearly three decades of searching for a vaccine against HIV, a cure for this pandemic disease still remains elusive. The low immunogenicity of the surface proteins and the huge variability of the virus, together with the immunocompromised status of the host, have made developing an HIV vaccine an uphill battle. Over the past few years, both immunogen design and immunization strategies have improved, providing hope for future, although the anti-HIV responses achieved still remain modest. As developing a prophylactic vaccine seems unlikely nowadays, efforts have focused on alternative therapeutic immunization approaches, although these still need to be further optimized. Using an immunomodulator capable of restoring immune function in the context of infection, thereby boosting cell-mediated and humoral responses, could be critical in effectively improving current therapeutic approaches. Adenosine deaminase, a protein with a pivotal role in T-cell co-stimulation, has been shown to robustly enhance specific T-cell responses against HIV in vitro. Although its role in humoral responses has not yet been assessed, genetic defects in this enzyme are associated with impaired cellular and humoral responses. Importantly, this molecule is already commercially available pharmaceutically and, therefore, it fulfils all the requirements to be assayed as an anti-HIV vaccine adjuvant. 相似文献
135.
Spatial patterns in brown bear Ursus arctos diet: the role of geographical and environmental factors
- 1 We reviewed worldwide spatial patterns in the food habits of the brown bear Ursus arctos in relation to geographical (latitude, longitude, altitude) and environmental (temperature, snow cover depth and duration, precipitation, primary productivity) variables.
- 2 We collected data from 28 studies on brown bear diet based on faecal analysis, covering the entire geographical range of this widely distributed large carnivore. We analysed separately four data sets based on different methods of diet assessment.
- 3 Temperature and snow conditions were the most important factors determining the composition of brown bear diet. Populations in locations with deeper snow cover, lower temperatures and lower productivity consumed significantly more vertebrates, fewer invertebrates and less mast. Trophic diversity was positively correlated with temperature, precipitation and productivity but negatively correlated with the duration of snow cover and snow depth. Brown bear populations from temperate forest biomes had the most diverse diet. In general, environmental factors were more explicative of diet than geographical variables.
- 4 Dietary spatial patterns were best revealed by the relative biomass and energy content methods of diet analysis, whereas the frequency of occurrence and relative biomass methods were most appropriate for investigating variation in trophic diversity.
- 5 Spatial variation in brown bear diet is the result of environmental conditions, especially climatic factors, which affect the nutritional and energetic requirements of brown bears as well as the local availability of food. The trade‐off between food availability on the one hand, and nutritional and energetic requirements on the other hand, determines brown bear foraging decisions. In hibernating species such as the brown bear, winter severity seems to play a role in determining foraging strategies. Large‐scale reviews of food habits should be based on several measures of diet composition, with special attention to those methods reflecting the energetic value of food.
136.
Ortega A Romero M Izquierdo A Troyano N Arce Y Ardura JA Arenas MI Bover J Esbrit P Bosch RJ 《Journal of cellular physiology》2012,227(5):1980-1987
Hypertrophy of human mesangial cells (HMC) is among the earliest characteristics in patients with diabetic nephropathy (DN). Recently, we observed the upregulation of parathyroid hormone (PTH)-related protein (PTHrP) in experimental DN, associated with renal hypertrophy. Herein, we first examined whether PTHrP was overexpressed in human DN, and next assessed the putative role of this protein on high glucose (HG)-induced HMC hypertrophy. As previously found in mice, kidneys from diabetic patients showed an increased tubular and glomerular immunostaining for PTHrP. In HMC, HG medium increased PTHrP protein expression associated with the development of hypertrophy as assessed by cell protein content. This effect was also induced by PTHrP(1-36). HG and PTHrP(1-36)-induced hypertrophy were associated with an increase in cyclin D1 and p27Kip1 protein expression, a decreased cyclin E expression, and the prevention of cyclin E/cdk2 complex activation. Both PTHrP neutralizing antiserum (α-PTHrP) and the PTH/PTHrP receptor antagonist (JB4250) were able to abolish HG induction of hypertrophy, the aforementioned changes in cell cycle proteins, and also TGF-β1 up-regulation. Moreover, the capability of both HG and PTHrP(1-36) to induce HMC hypertrophy was abolished by α-TGFβ1. These data show for the first time that PTHrP is upregulated in the kidney of patients with DN. Our findings also demonstrate that PTHrP acts as an important mediator of HG-induced HMC hypertrophy by modulating cell cycle regulatory proteins and TGF-β1. 相似文献
137.
Homer is a family of cytoplasmic adaptor proteins that play different roles in cell function, including the regulation of G-protein-coupled receptors. These proteins contain an Ena (Enabled)/VASP (vasodilator-stimulated phosphoprotein) homology 1 domain that binds to the PPXXF sequence motif, which is present in different Ca2?-handling proteins such as IP3 (inositol 1,4,5-trisphosphate) receptors and TRPC (transient receptor potential canonical) channels. In the present study we show evidence for a role of Homer proteins in the STIM1 (stromal interaction molecule 1)-Orai1 association, as well as in the TRPC1-IP3RII (type II IP3 receptor) interaction, which might be of relevance in platelet function. Treatment of human platelets with thapsigargin or thrombin results in a Ca2?-independent association of Homer1 with TRPC1 and IP3RII. In addition, thapsigargin and thrombin enhanced the association of Homer1 with STIM1 and Orai1 in a Ca2?-dependent manner. Interference with Homer function by introduction of the synthetic PPKKFR peptide into cells, which emulates the proline-rich sequences of the PPXXF motif, reduced STIM1-Orai1 and TRPC1- IP3RII associations, as compared with the introduction of the inactive PPKKRR peptide. The PPKKFR peptide attenuates thrombin-evoked Ca2? entry and the maintenance of thapsigargin-induced store-operated Ca2? entry. Finally, the PPKKFR peptide attenuated thrombin-induced platelet aggregation. The findings of the present study support an important role for Homer proteins in thrombin-stimulated platelet function, which is likely to be mediated by the support of agonist-induced Ca2? entry. 相似文献
138.
139.
Marín PJ Santos-Lozano A Santin-Medeiros F Vicente-Rodriguez G Casajús JA Hazell TJ Garatachea N 《Journal of electromyography and kinesiology》2012,22(3):456-462
The current study examined the effects of whole-body vibration (WBV) on upper and lower body muscle activity during static muscle contractions (squat and bicep curls). The use of WBV accessories such as hand straps attached to the platform and a soft surface mat were also evaluated. Surface electromyography (sEMG) was measured for the medial gastrocnemius (MG), vastus lateralis (VL), and biceps brachii (BB) muscles in fourteen healthy older adults (74.8±4.5 years; mean±SD) with a WBV stimulus at an acceleration of 40 m s(-2) (30 Hz High, 2.5 mm or 46 Hz Low, 1.1 mm). WBV increased lower body (VL and MG) sEMG vs baseline (no WBV) though this was decreased with the use of the soft mat. The addition of the bicep curl with hand straps had no effect on lower body sEMG. WBV also increased BB sEMG vs baseline which was further increased when using the hand straps. There was no upper body effect of the soft mat. This study demonstrates WBV increases both lower and upper body muscle activity in healthy older adults. Moreover, WBV accessories such as hand straps attached to the platform or a soft surface mat may be used to alter exercise intensity. 相似文献
140.
Nuria Selva Keith A. Hobson Ainara Cortés-Avizanda Andrzej Zalewski José Antonio Donázar 《PloS one》2012,7(12)
How different functional responses of consumers exploiting pulsed resources affect community dynamics is an ongoing question in ecology. Tree masting is a common resource pulse in terrestrial ecosystems that can drive rodent population cycles. Using stable isotope (δ13C, δ15N) analyses, we investigated the dietary response of two fluctuating rodent species, the yellow-necked mouse Apodemus flavicollis and the bank vole Myodes glareolus, to mast events in Białowieża Forest (NE Poland). Rodent hair samples were obtained non-invasively from faeces of their predators for an 11-year period that encompassed two mast events. Spectacular seed crops of deciduous trees, namely oak Quercus robur and hornbeam Carpinus betulus, occur after several intermediate years of moderate seed production, with a post-mast year characterised by a nil crop. While a Bayesian isotopic (SIAR) mixing model showed a variety of potential vegetation inputs to rodent diets, the isotopic niche of the yellow-necked mouse was strongly associated with mast of deciduous trees (>80% of diet), showing no variation among years of different seed crop. However, bank voles showed a strong functional response; in mast years the vole shifted its diet from herbs in deciduous forest (∼66% of diet) to mast (∼74%). Only in mast years did the isotopic niche of both rodent species overlap. Previous research showed that bank voles, subordinate and more generalist than mice, showed higher fluctuations in numbers in response to masting. This study provides unique data on the functional response of key pulse consumers in forest food webs, and contributes to our understanding of rodent population fluctuations and the mechanisms governing pulse–consumer interactions. 相似文献