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171.
Farina AR Cappabianca L Di Ianni N Ruggeri P Ragone M Merolle S Gulino A Mackay AR 《FEBS letters》2012,586(16):2366-2374
Irreversible MMP-9 inhibition is considered a significant therapeutic goal in inflammatory, vascular and tumour pathology. We report that divalent cation chelators Alendronate and EDTA not only directly inhibited MMP-9 but also promoted irreversible plasmin-mediated MMP-9 inactivation by exposing cryptic plasmin-degradation sites within the MMP-9 catalytic-domain and producing an inhibitory hemopexin-domain fragment. This effect was also observed using MDA-MB-231 breast cancer cells, which activated exogenous plasminogen to degrade endogenous proMMP-9 in the presence of Alendronate or EDTA. Degradation-mediated inactivation of proMMP-9 occurred in the absence of transient activation, attesting to the incapacity of plasmin to directly activate proMMP-9 and direct MMP-9 inhibition by Alendronate and EDTA. Our study provides a novel rational for therapeutic Alendronate use in MMP-9-dependent pathology characterised by plasminogen activation. 相似文献
172.
Magali Lucia Jean-Marc Andre Patrice Gonzalez Magalie Baudrimont Karine Gontier Regine Maury-Brachet Stephane Davail 《Biometals》2009,22(5):843-853
The impact on palmiped Cairina moschata of two levels of dietary cadmium (Cd) contamination (C1: 1 mg kg−1 and C10: 10 mg kg−1) was investigated on liver gene expression by real-time PCR. Genes involved in mitochondrial metabolism, in antioxidant defences,
detoxification and in DNA damage repair were studied. Metallothionein (MT) protein levels and Cd bioaccumulation were also
investigated in liver, kidneys and muscle. Male ducks were subjected to three periods of exposure: 10, 20 and 40 days. Cd
was mainly bioaccumulated in kidneys first and in liver. The concentrations in liver and kidneys appeared to reach a stable
level at 20 days of contamination even if the concentrations in muscle still increased. Cd triggered the enhancement of mitochondrial
metabolism, the establishment of antioxidant defences (superoxide dismutase Mn and Cu/Zn; catalase) and of DNA repair from
20 days of contamination. Discrepancies were observed in liver between MT protein levels and MT gene up-regulation. MT gene
expression appeared to be a late hour biomarker. 相似文献
173.
P. Cugini G. Leone P. Lucia F. A. Sepe A. Pelosio T. Caparrelli R. Verardi A. Zannella P. Zannella G. Pannozzo F. Di Fonzo F. P. Zannella 《Chronobiology international》1994,11(6):381-392
Noninvasive ambulatory blood pressure (BP) monitoring is a developing method in clinical practice. Its interpretation needs reference standards stratified by age and gender. This study addresses ambulatory BP monitoring in elderly people with the purpose of quantifying the discrete and periodic variability of BP pattern over a 24-h period. The ABPM was performed in 92 clinically healthy subjects (45 men and 47 women) ranging in age from 76 to 102 years. The results refer to the time-qualified mean values with their dispersion, to the circadian rhythm with its parameters, and to the daily baric impact (BI) with its variability. The conclusion is drawn that BP preserves its nychtohemeral variability and circadian rhythmicity despite old age. The daily BP mean level and BI in older people in good health are comparable with those of young subjects, suggesting that humans surviving into old age are characterized by a eugenic control of their pressure regimen. 相似文献
174.
Brunetti L Orlando G Recinella L Leone S Ferrante C Chiavaroli A Lazzarin F Vacca M 《Peptides》2008,29(8):1377-1381
Glucagon-like peptide 1 (7-36) amide (GLP-1) and exendin-4 are gastrointestinal hormones as well as neuropeptides involved in glucose homeostasis and feeding regulation, both peripherally and at the central nervous system (CNS), acting through the same GLP-1 receptor. Aminergic neurotransmitters play a role in the modulation of feeding in the hypothalamus and we have previously found that peripheral hormones and neuropeptides, which are known to modulate feeding in the central nervous system, are able to modify catecholamine and serotonin release in the hypothalamus. In the present paper we have evaluated the effects of GLP-1 and exendin-4 on dopamine, norepinephrine, and serotonin release from rat hypothalamic synaptosomes, in vitro. We found that glucagon-like peptide 1 (7-36) amide and exendin-4 did not modify either basal or depolarization-induced dopamine and norepinephrine release; on the other hand glucagon-like peptide 1 (7-36) amide and exendin-4 stimulated serotonin release, in a dose dependent manner. We can conclude that the central anorectic effects of GLP-1 agonists could be partially mediated by increased serotonin release in the hypothalamus, leaving the catecholamine release unaffected. 相似文献
175.
176.
De Stefano L Vitale A Rea I Staiano M Rotiroti L Labella T Rendina I Aurilia V Rossi M D'Auria S 《Extremophiles : life under extreme conditions》2008,12(1):69-73
The D-trehalose/D-maltose-binding protein (TMBP), a monomeric protein of 48 kDa, is one component of the trehalose and maltose
(Mal) uptake system. In the hyperthermophilic archaeon Thermococcus litoralis, this is mediated by a protein-dependent ATP-binding cassette system transporter. The gene coding for a thermostable TMBP
from the archaeon T. litoralis has been cloned, and the recombinant protein has been expressed in E. coli. The recombinant TMBP has been purified to homogeneity and characterized. It exhibits the same functional and structural
properties as the native one. In fact, it is highly thermostable and binds sugars, such as maltose, trehalose and glucose,
with high affinity. In this work, we have immobilized TMBP on a porous silicon wafer. The immobilization of TMBP to the chip
was monitored by reflectivity and Fourier Transformed Infrared spectroscopy. Furthermore, we have tested the optical response
of the protein-Chip complex to glucose binding. The obtained data suggest the use of this protein for the design of advanced
optical non-consuming analyte biosensors for glucose detection.
The authors wish to dedicate this work to Prof. Ignacy Gryczynski, University of North Texas, TX, USA, for his outstanding
contribution to the development of new sensing methodologies. 相似文献
177.
178.
Cutting edge: a naturally occurring mutation in CD1e impairs lipid antigen presentation 总被引:1,自引:0,他引:1
Tourne S Maitre B Collmann A Layre E Mariotti S Signorino-Gelo F Loch C Salamero J Gilleron M Angénieux C Cazenave JP Mori L Hanau D Puzo G De Libero G de la Salle H 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(6):3642-3646
The human CD1a-d proteins are plasma membrane molecules involved in the presentation of lipid Ags to T cells. In contrast, CD1e is an intracellular protein present in a soluble form in late endosomes or lysosomes and is essential for the processing of complex glycolipid Ags such as hexamannosylated phosphatidyl-myo-inositol, PIM(6). CD1e is formed by the association of beta(2)-microglobulin with an alpha-chain encoded by a polymorphic gene. We report here that one variant of CD1e with a proline at position 194, encoded by allele 4, does not assist PIM(6) presentation to CD1b-restricted specific T cells. The immunological incompetence of this CD1e variant is mainly due to inefficient assembly and poor transport of this molecule to late endosomal compartments. Although the allele 4 of CD1E is not frequent in the population, our findings suggest that homozygous individuals might display an altered immune response to complex glycolipid Ags. 相似文献
179.
Felitsyn N McLeod C Shroads AL Stacpoole PW Notterpek L 《Journal of neurochemistry》2008,106(5):2068-2079
Delta-aminolevulinic acid (δ-ALA) is a heme precursor implicated in neurological complications associated with porphyria and tyrosinemia type I. Delta-ALA is also elevated in the urine of animals and patients treated with the investigational drug dichloroacetate (DCA). We postulated that δ-ALA may be responsible, in part, for the peripheral neuropathy observed in subjects receiving DCA. To test this hypothesis, myelinating cocultures of Schwann cells and sensory neurons were exposed to δ-ALA (0.1–1 mM) and analyzed for the expression of neural proteins and lipids and markers of oxidative stress. Exposure of myelinating samples to δ-ALA is associated with a pronounced reduction in the levels of myelin-associated lipids and proteins, including myelin protein zero and peripheral myelin protein 22. We also observed an increase in protein carbonylation and the formation of hydroxynonenal and malondialdehyde after treatment with δ-ALA. Studies of isolated Schwann cells and neurons indicate that glial cells are more vulnerable to this pro-oxidant than neurons, based on a selective decrease in the expression of mitochondrial respiratory chain proteins in glial, but not in neuronal, cells. These results suggest that the neuropathic effects of δ-ALA are attributable, at least in part, to its pro-oxidant properties which damage myelinating Schwann cells. 相似文献
180.
Lucia Vernerova Frantisek Spoutil Miroslav Vlcek Katarina Krskova Adela Penesova Milada Meskova Andrea Marko Katarina Raslova Branislav Vohnout Jozef Rovensky Zdenko Killinger Ivana Jochmanova Ivica Lazurova Guenter Steiner Josef Smolen Richard Imrich 《PloS one》2016,11(4)
IntroductionThe aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA) and redundancy analysis (RDA).MethodsA total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE) in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601), STAT4 G/T (rs7574865), CTLA4 A/G (rs3087243), TRAF1/C5 A/G (rs3761847), IRF5 T/C (rs10488631), TNFAIP3 C/T (rs5029937), AFF3 A/T (rs11676922), PADI4 C/T (rs2240340), CD28 T/C (rs1980422), CSK G/A (rs34933034) and FCGR3A A/C (rs396991), rheumatoid factor (RF), anti–citrullinated protein antibodies (ACPA) and clinical status was analysed using the LDA and RDA.ResultsHLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002). The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001). The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA.ConclusionsThe association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA. 相似文献