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91.
92.
Pagé D Balaux E Boisvert L Liu Z Milburn C Tremblay M Wei Z Woo S Luo X Cheng YX Yang H Srivastava S Zhou F Brown W Tomaszewski M Walpole C Hodzic L St-Onge S Godbout C Salois D Payza K Payza K 《Bioorganic & medicinal chemistry letters》2008,18(13):3695-3700
The preparation and evaluation of a novel class of CB2 agonists based on a benzimidazole moiety are reported. They showed binding affinities up to 1nM towards the CB2 receptor with partial to full agonist potencies. They also demonstrated good to excellent selectivity (>1000-fold) over the CB1 receptor. 相似文献
93.
Frederique Zindy Youngsoo Lee Daisuke Kawauchi Olivier Ayrault Leila Ben Merzoug Yang Li Peter J. McKinnon Martine F. Roussel 《PloS one》2015,10(6)
Dicer, a ribonuclease III enzyme, is required for the maturation of microRNAs. To assess its role in cerebellar and medulloblastoma development, we genetically deleted Dicer in Nestin-positive neural progenitors and in mice lacking one copy for the Sonic Hedgehog receptor, Patched 1. We found that conditional loss of Dicer in mouse neural progenitors induced massive Trp53-independent apoptosis in all proliferative zones of the brain and decreased proliferation of cerebellar granule progenitors at embryonic day 15.5 leading to abnormal cerebellar development and perinatal lethality. Loss of one copy of Dicer significantly accelerated the formation of mouse medulloblastoma of the Sonic Hedgehog subgroup in Patched1-heterozygous mice. We conclude that Dicer is required for proper cerebellar development, and to restrain medulloblastoma formation. 相似文献
94.
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
95.
In this paper, partitioning behaviors of typical neutral (Alanine), acidic (Glutamic acid) and basic (Lysine) amino acids
into imidazolium-based ionic liquids [C4mim][PF6], [C6mim][PF6], [C8mim][PF6], [C6mim][BF4] and [C8mim][BF4] as extracting solvents were examined. [C6mim][BF4] showed the best efficiency for partitioning of amino acids. The partition coefficients of amino acids in ionic liquids were
found to depend strongly on pH of the aqueous solution, amino acid and ionic liquid chemical structures. Different chemical
forms of amino acids in aqueous solutions were pH dependent, so the pH value of the aqueous phase was a determining factor
for extraction of amino acids into ionic liquid phase. Both water content of ionic liquids and charge densities of their anionic
and cationic parts were important factors for partitioning of cationic and anionic forms of amino acids into ionic liquid
phase. Extracted amino acids were back extracted into phosphate buffer solutions adjusted on appropriate pH values. The results
showed that ionic liquids could be used as suitable modifiers on the stationary phase of an HPLC column for efficient separation
of acidic, basic, and neutral amino acids. 相似文献
96.
Gholamreza Bahrami Bahareh Mohammadi Pyman Malek Khatabi Mohammad Hosein Farzaei Mohammad Bagher Majnooni Saba Rahimi Bahoosh 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(28):2789-2795
A new one-step liquid chromatography–electrospray tandem MS/MS method is described to quantify ezetimibe (EZM) a novel lipid lowering drug in human serum. Also using collision-induced dissociation (CID) of the analyte, identification and chromatographic separation of its major metabolite, ezetimibe glucuronide (EZM-G) is achieved in this study. A thawed serum aliquot of 100 μL was deproteinated by addition of 500 μL methanol containing omeprazole as internal standard (I.S.). Separation of the drug, its metabolite and the I.S. were achieved using acetonitrile–water (70:30, v/v) as mobile phase at flow rate of 0.5 mL/min on a MZ PerfectSil target C18 column. Multiple reaction monitoring (MRM) mode of precursor–product ion transition (408.7 → 272.0 for EZM and 345 → 194.5 for the I.S.) was applied for detection and quantification of the drug while, EZM-G was chromatographically separated and identified using CID. The analytical method was linear over the concentration range of 1–32 ng/mL of EZM in human serum with a limit of quantification of 1 ng/mL. The coefficient variation values of both inter- and intra-day analysis were less than 8% whereas the percentage error was less than 3.7. The validated method was applied in a randomized cross-over bioequivalence study of two different EZM preparations in 24 healthy volunteers. 相似文献
97.
Mohamed Ben Sghaier Jihed Boubaker Aicha Neffati Ilef Limem Ines Skandrani Wissem Bhouri Ines Bouhlel Soumaya Kilani Leila Chekir‐Ghedira Kamel Ghedira 《化学与生物多样性》2010,7(7):1754-1763
The mutagenic and antimutagenic effects of the essential oil extracted from the aerial parts of Teucrium ramosissimum were evaluated by the bacterial reverse mutation assay in Salmonella typhimurium TA98, TA100, and TA1535, with and without exogenous metabolic activation (S9 fraction). The T. ramosissimum essential oil showed no mutagenic effect. In contrast, our results established that it possessed antimutagenic effects against sodium azide (SA), aflatoxin B1 (AFB1), benzo[a]pyrene (B[a]P), and 4‐nitro‐o‐phenylenediamine (NOPD). The antioxidant capacity of the tested essential oil was evaluated using enzymatic, i.e., the xanthine/xanthine oxidase (X/XOD) assay, and nonenzymatic systems, i.e., the nitro‐blue tetrazolium (NBT)/riboflavin and the DPPH assays. A moderate free radical‐scavenging activity was observed towards DPPH. and O$\rm{{_{2}^{{^\cdot} -}}}$ . In contrast, T. ramosissimum essential oil showed no effect for all the tested concentrations in the X/XOD assay. 相似文献
98.
Leila M. Luheshi Wolfgang Hoyer Teresa Pereira de Barros Iris van Dijk H?rd Ann-Christin Brorsson Bertil Macao Cecilia Persson Damian C. Crowther David A. Lomas Stefan St?hl Christopher M. Dobson Torleif H?rd 《PLoS biology》2010,8(3)
Protein aggregation, arising from the failure of the cell to regulate the synthesis or degradation of aggregation-prone proteins, underlies many neurodegenerative disorders. However, the balance between the synthesis, clearance, and assembly of misfolded proteins into neurotoxic aggregates remains poorly understood. Here we study the effects of modulating this balance for the amyloid-beta (Aβ) peptide by using a small engineered binding protein (ZAβ3) that binds with nanomolar affinity to Aβ, completely sequestering the aggregation-prone regions of the peptide and preventing its aggregation. Co-expression of ZAβ3 in the brains of Drosophila melanogaster expressing either Aβ42 or the aggressive familial associated E22G variant of Aβ42 abolishes their neurotoxic effects. Biochemical analysis indicates that monomer Aβ binding results in degradation of the peptide in vivo. Complementary biophysical studies emphasize the dynamic nature of Aβ aggregation and reveal that ZAβ3 not only inhibits the initial association of Aβ monomers into oligomers or fibrils, but also dissociates pre-formed oligomeric aggregates and, although very slowly, amyloid fibrils. Toxic effects of peptide aggregation in vivo can therefore be eliminated by sequestration of hydrophobic regions in monomeric peptides, even when these are extremely aggregation prone. Our studies also underline how a combination of in vivo and in vitro experiments provide mechanistic insight with regard to the relationship between protein aggregation and clearance and show that engineered binding proteins may provide powerful tools with which to address the physiological and pathological consequences of protein aggregation. 相似文献
99.
Leila Roufegarinejad Ryszard Amarowicz 《Journal of biomolecular structure & dynamics》2019,37(11):2766-2775
In the present study, the interaction of Pyrogallol (PG) with human serum albumin (HSA) was investigated by UV, fluorescence, Circular dichroism (CD), and molecular docking methods. The results of fluorescence experiments showed that the quenching of intrinsic fluorescence of HSA by PG was due to a static quenching. The calculated binding constants (K) for PG-HSA at different temperatures were in the order of 104?M ?1, and the corresponding numbers of binding sites, n were approximately equal to unity. The thermodynamic parameters, ΔH and ΔS were calculated to be negative, which indicated that the interaction of PG with HSA was driven mainly by van der Waals forces and hydrogen bonds. The negative value was obtained for ΔG showed that the reaction was spontaneous. In addition, the effect of PG on the secondary structure of HSA was analyzed by performing UV–vis, synchronous fluorescence, and CD experiments. The results indicated that PG induced conformational changes in the structure of HSA. According to Förster no-radiation energy transfer theory, the binding distance of HSA to PG was calculated to be 1.93?nm. The results of molecular docking calculations clarified the binding mode and the binding sites which were in good agreement with the results of experiments.
Communicated by Ramaswamy H. Sarma 相似文献
100.
Sara Jafarzadeh Majid Ahmadi Sanam Dolati Leili Aghebati-Maleki Shadi Eghbal-Fard Amin Kamrani Behboud Behrad Leila Roshangar Farhad Jadidi-Niaragh Bahman Yousefi Mahdi Mehdipour Laya Farzadi Mehdi Yousefi 《Journal of cellular biochemistry》2019,120(4):5424-5434
Exhausted T cells and regulatory T (Treg) cells have been recently proposed to be new risk factors for recurrent miscarriage (RM). Intravenous immunoglobulin G (IVIG) treatment reported to modulate various immune cells. In this study, the effects of IVIG on the frequency and function of exhausted T cells, exhausted Tregs, and Treg cells, as well as pregnancy outcome in women with unexplained RM (URM), were investigated. Ninety-four pregnant women with RM were enrolled. At the time of positive pregnancy, blood samples were drawn. Forty-four patients with URM were included as IVIG receiving treated group and received 400 mg/kg of IVIG and the rest fifty patients were considered as a control group and received no IVIG administration. IVIG was given intravenously every 4 weeks during 32 weeks of gestation. Blood samples of patients were collected after the latest administration. Exhausted T cells, exhausted Tregs, and Treg cells were evaluated pre- and posttreatment in both groups. IVIG induced a significant decrease in the frequency of exhausted Tregs population and function as well as a significant increase in Treg cells population, however, IVIG failed to affect population and the function of exhausted T cells. Pregnancy outcome was successful in IVIG treated women (86.3%) and were significantly different (P = 0.0006) in compared with the untreated URM subjects (42%). Therefore, employing of IVIG increases Treg cells and diminishes exhausted Tregs responses in RM patients with cellular immune anomalies throughout the pregnancy. Immunemodulatory effects of IVIG are probably associated with successful pregnancy outcome. 相似文献