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142.
Omar EstradaJuan Manuel González-Guzmán Margarita Salazar-BookamanAna Z. Fernández Alfonso CardozoClaudia Alvarado-Castillo 《Phytomedicine》2011,18(6):464-469
Pomolic acid has recently shown hypotensive effect in rats. The purpose of this investigation was to determine the vascular effects of this triterpenoid and to examine its mode of action. Functional experiments in rat aortic rings precontracted with norepinephrine were performed to evaluate the vasorelaxant effect of pomolic acid. This triterpenoid induced a vasorelaxation (IC50 = 2.45 μM) in a concentration- and endothelium-dependent manner and showed no effect on contractions evoked by KCl (25 mM). Pre-treatment of aortic rings with l-NAME (100 μM), methylene blue (100 μM) or glibenclamide (10 μM), totally prevented the vasorelaxation induced by pomolic acid, while indomethacin (10 μM) had no effect on this response. Additionally, pomolic acid relaxation was unaffected under the muscarinic- and β-adrenergic-receptor blocked ensured for atropine and propanolol respectively (10 μM each). In contrast, the vasorelaxant effect of pomolic acid was abolished under the purinergic-receptor blocked ensured for suramin (10 μM). Finally, apyrase (0.8 U/ml) an enzyme which hydrolyses ATP and ADP did not affect pomolic acid relaxation. In summary, pomolic acid has a potent endothelium-dependent vasorelaxant effect, possibly acting through the direct activation of endothelial purinergic receptors via NO-cGMP signaling pathway, which could be part of the mechanism underlying its hypotensive effect. 相似文献
143.
Ramelteon, an MT(1)/MT(2) melatonin receptor agonist, is used for the treatment of sleep-onset insomnia and circadian sleep disorders. Ramelteon phase shifts circadian rhythms in rodents and humans when given at the end of the subjective day; however, its efficacy at other circadian times is not known. Here, the authors determined in C3H/HeN mice the maximal circadian sensitivity for ramelteon in vivo on the onset of circadian running-wheel activity rhythms, and in vitro on the peak of circadian rhythm of neuronal firing in suprachiasmatic nucleus (SCN) brain slices. The phase response curve (PRC) for ramelteon (90?μg/mouse, subcutaneous [sc]) on circadian wheel-activity rhythms shows maximal sensitivity during the late mid to end of the subjective day, between CT8 and CT12 (phase advance), and late subjective night and early subjective day, between CT20 and CT2 (phase delay), using a 3-day-pulse treatment regimen in C3H/HeN mice. The PRC for ramelteon resembles that for melatonin in C3H/HeN mice, showing the same magnitude of maximal shifts at CT10 and CT2, except that the range of sensitivity for ramelteon (CT8-CT12) during the subjective day is broader. Furthermore, in SCN brain slices in vitro, ramelteon (10 pM) administered at CT10 phase advances (5.6?±?0.29?h, n?=?3) and at CT2 phase delays (-3.2?±?0.12?h, n?=?6) the peak of circadian rhythm of neuronal firing, with the shifts being significantly larger than those induced by melatonin (10 pM) at the same circadian times (CT10: 2.7?±?0.15?h, n?=?4, p?.05; CT2: -1.13?±?0.08?h, n?=?6, p?.001, respectively). The phase shifts induced by both melatonin and ramelteon in the SCN brain slice at either CT10 or CT2 corresponded with the period of sensitivity observed in vivo. In conclusion, melatonin and ramelteon showed identical periods of circadian sensitivity at CT10 (advance) and CT2 (delay) to shift the onset of circadian activity rhythms in vivo and the peak of SCN neuronal firing rhythms in vitro. 相似文献
144.
Infantes S Lorente E Cragnolini JJ Ramos M García R Jiménez M Iborra S Del Val M López D 《Immunology and cell biology》2011,89(4):558-565
Short viral antigens bound to human major histocompatibility complex (HLA) class I molecules are presented on infected cells. Vaccine development frequently relies on synthetic peptides to identify optimal HLA class I ligands. However, when natural peptides are analyzed, more complex mixtures are found. By immunoproteomics analysis, we identify in this study a physiologically processed HLA ligand derived from the human respiratory syncytial virus matrix protein that is very different from what was expected from studies with synthetic peptides. This natural HLA-Cw4 class I ligand uses alternative interactions to the anchor motifs previously described for its presenting HLA-Cw4 class I molecule. Finally, this octameric peptide shares its C-terminal core with the H-2D(b) nonamer ligand previously identified in the mouse model. These data have implications for the identification of antiviral cytotoxic T lymphocyte responses and for vaccine development. 相似文献
145.
Watson C Owen DR Harding D Kon-I K Lewis ML Mason HJ Matsumizu M Mukaiyama T Rodriguez-Lens M Shima A Takeuchi M Tran I Young T 《Bioorganic & medicinal chemistry letters》2011,21(14):4284-4287
A series of benzimidazole CB2 receptor agonists were prepared and their properties investigated. Optimisation of the three benzimidazole substituents led to the identification of compound 23, a potent CB2 full agonist (EC50 2.7 nM) with excellent selectivity over the CB1 receptor (>3000-fold). Compound 23 demonstrated good CNS penetration in rat. Further optimisation led to the identification of compound 34 with improved selectivity over hERG and excellent CNS penetration in rat. 相似文献
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CD4(+)CD25(high)CD127(low/-) forkhead box p3 (Foxp3)(+) regulatory T cells (T(reg) cells) possess functional plasticity. Here we describe a higher frequency of T helper type 1 (T(H)1)-like, interferon-γ (IFN-γ)-secreting Foxp3(+) T cells in untreated subjects with relapsing remitting multiple sclerosis (RRMS) as compared to healthy control individuals. In subjects treated with IFN-β, the frequency of IFN-γ(+)Foxp3(+) T cells is similar to that in healthy control subjects. In vitro, human T(reg) cells from healthy subjects acquire a T(H)1-like phenotype when cultured in the presence of interleukin-12 (IL-12). T(H)1-like T(reg) cells show reduced suppressive activity in vitro, which can partially be reversed by IFN-γ-specific antibodies or by removal of IL-12. 相似文献
149.
Roodenburg AJ Schlatmann A Dötsch-Klerk M Daamen R Dong J Guarro M Stergiou M Sayed N Ronoh E Jansen L Seidell JC 《PloS one》2011,6(2):e14721
Introduction
Nutrient profiling is defined as the science of categorising foods based on their nutrient composition. The Choices Programme is a nutrient profile system with criteria that determine whether foods are eligible to carry a “healthier option” stamp. The Daily Menu Method which has been developed to evaluate these criteria is described here. This method simulates the change in calculated nutrient intakes which would be the result of consumers changing their diets in favour of food products that comply with the criteria.Methods
Average intakes of energy, trans fatty acids (TFA), saturated fatty acids (SAFA), sodium, added sugar and fibre were derived from dietary intake studies and food consumption surveys of 7 countries: The Netherlands, Greece, Spain, the USA, Israel, China and South Africa. For each of the key nutrients, these average intakes were translated into three Typical Daily Menus per country. Average intakes based on these three menus were compared with average intakes from three Choices Daily Menus. To compose the Choices Menus, foods from the Typical Menus that did not comply with the Choices criteria were replaced with foods that did comply and are available on the market.Results
Comparison of intakes from the Choices Menus with the survey data showed that calculated intakes of energy, SAFA, TFA, sodium and added sugar were reduced. Fibre intakes were increased. The size of the effect differed per country.Conclusion
The Daily Menu Method is a useful means to predict the potential effects of nutrient profiles such as the Choices criteria, on daily nutrient intakes. The method can be applied internationally and confirms that the criteria of the Choices Programme are in line with the aim of the programme: to improve nutrient intakes in the direction of the recommendations. 相似文献150.
Guaderrama-Díaz M Solís CF Velasco-Loyden G Laclette JP Mas-Oliva J 《Molecular and cellular biochemistry》2005,271(1-2):123-132
The scavenger receptor recognized as a multiligand family of receptors falls in the group that is internalised through endocytosis. In this report we used several recombinant fragments of the tapeworm protein paramyosin, known to form filamentous dimers that bind collagenous structures as ligands of different length for the class A type I scavenger receptor (SR-AI). While native CHO cells are unresponsive to any of the recombinant fragments, it is shown that CHO cells transfected with this receptor efficiently internalise recombinant fragments that correspond to two thirds of the full-length paramyosin. In contrast, recombinant products corresponding to one-third of the full-length paramyiosin are not internalised. It is also shown that important molecules in the organization of the coated pit, are enriched when the two-thirds long paramyosin fragments were bound and internalised through the SR-AI. Moreover, internalisation of these fragments trigger a classical apoptotic pathway shown by the presence of TUNEL positive cells and the appearance of apoptotic bodies. We report paramyosin as a new ligand for the scavenger receptor and provide evidence supporting the notion that these receptors upon the formation of arrays with length-specific molecules, not only trigger endocytosis but also seem to regulate the synthesis of molecules involved in the organization of coated pits. (Mol Cell Biochem 271: 123–132, 2005) 相似文献