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101.
102.
Julie A. Eclov Qingwen Qian Rebecca Redetzke Quanhai Chen Steven C. Wu Chastity L. Healy Steven B. Ortmeier Erin Harmon Gregory C. Shearer Timothy D. O’Connell 《Journal of lipid research》2015,56(12):2297-2308
Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor β1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF. 相似文献
103.
104.
《Journal of molecular recognition : JMR》2017,30(3)
Heparin‐induced thrombocytopenia (HIT), occurring up to approximately 1% to 5% of patients receiving the antithrombotic drug heparins, has a complex pathogenesis involving multiple partners ranging from small molecules to cells/platelets. Recently, insights into the mechanism of HIT have been achieved by using single‐molecule force spectroscopy (SMFS), a methodology that allows direct measurements of interactions among HIT partners. Here, the potential of SMFS in unraveling the mechanism of the initial steps in the pathogenesis of HIT at single‐molecule resolution is highlighted. The new findings ranging from the molecular binding strengths and kinetics to the determination of the boundary between risk and non‐risk heparin drugs or platelet‐surface and platelet‐platelet interactions will be reviewed. These novel results together have contributed to elucidate the mechanisms underlying HIT and demonstrate how SMFS can be applied to develop safer drugs with a reduced risk profile. 相似文献
105.
《Peptides》2014
The frog skin host-defense peptide tigerinin-1R (RVCSAIPLPICH.NH2) is insulinotropic both in vitro and in vivo. This study investigates the effects on insulin release and cytotoxicity of changes in cationicity and hydrophobicity produced by selected substitutions of amino acids by l-arginine, l-lysine and l-tryptophan. The [A5W], [L8W] and [I10W] analogs produced a significant (P < 0.01) increase in the rate of insulin release from BRIN-BD11 rat clonal β cells at concentration of 0.01 nM compared with 0.1 nM for tigerinin-1R. The increase in the rate of insulin release produced by a 3 μM concentration of the [S4R], [H12K], and [I10W] analogs from both BRIN-BD11 cells and mouse islets was significantly greater (P < 0.05) than that produced by tigerinin-1R. No peptide stimulated the release of lactate dehydrogenase at concentrations up to 3 μM indicating that plasma membrane integrity had been preserved. [A5W] tigerinin-1R was the only analog tested that showed cytotoxic activity against human erythrocytes (LC50 = 265 ± 16 μM) and inhibited growth of Escherichia coli (MIC = 500 μM) and Staphylococcus aureus (MIC = 250 μM). The circular dichroism spectra of tigerinin-1R and [A5W] tigerinin-1R indicate that the peptides adopt a mixture of β-sheet, random coil and reverse β-turn conformations in 50% trifluoroethanol/water and methanol/water. Administration of [S4R] tigerinin-1R (75 nmol/kg body weight) to high-fat fed mice with insulin resistance significantly (P < 0.05) enhanced insulin release and improved glucose tolerance over a 60 min period following an intraperitoneal glucose load. The study supports the claim that tigerinin-1R shows potential for development into novel therapeutic agents for treatment of type 2 diabetes mellitus. 相似文献
106.
F. Berthault P. Kintz P. Mangin 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1996,685(2):1381
A high-performance liquid chromatographic method for the simultaneous determination of flunitrazepam and four metabolites, desmethylflunitrazepam (DMF), 7-aminodesmethylflunitrazepam (7-NH2DMF), 7-aminoflunitrazepam (7-NH2F) and 3-hydroxyflunitrazepam (3-OHF), in serum is described. The method involves a simple extraction from alkalinized plasma (pH 9.5) into diethyl ether-chloroform (80:20, v/v). Prazepam was used as an internal standard for the quantification of the five compounds. Separation was achieved with a 10 μm RSil CN column (300×3.9 mm I.D.). The detection wavelength was set at 242 nm. The limits of detection ranged from 2.5 to 5 μg/l with a limit of quantification of 10 μg/l for all analytes. 相似文献
107.
P. Pellegrini Anna Maria Berghella T. Del Beato Sergio Cicia Domenico Adorno Carlo Umberto Casciani 《Cancer immunology, immunotherapy : CII》1996,42(1):1-8
Recent theories have established that, during an ongoing immune response, the lymphokines produced by TH1 and TH2 subsets
of CD4+ T cells are critical to the effectiveness of that response. In vivo and in vitro studies have demonstrated that the type
of environmental cytokines plays a determinant role in directing the development of naive T cells into TH1 or TH2 effector
cells. Disregulated expansion of one or other subset may contribute to the development of certain diseases. To establish whether
a similar situation might exist in the cells of the peripheral blood (PBMC) of colorectal cancer patients, we have performed
immunological studies on a group of patients and a group of healthy subjects. We examined the interleukin-2 (IL-2), interferon
γ (IFNγ), IL-4, IL-6 and tumour necrosis factor α levels in serum; the production of IL-4 and IL-2, with and without activating
agents, by PBMC, tumour-draining lymph node lymphocytes and tumour cells; and the proliferative response of PBMC to IL-2,
IL-4 and anti-CD3 monoclonal antibody (anti-CD3), which were variously combined. The data of the present study lead us to
hypothesize that, because of suppressive effects probably due to environmental IL-4, in the peripheral blood of patients there
seems to be a disregulation in the functionality of TH1 and TH2 subsets of CD4+ T cells, with an expansion in TH2 and a malfunction in TH1 cells. Moreover it seems that this disregulation increases with
as the disease progresses through the stages, suggesting that it can be directly implicated in the mechanisms that allow the
tumour to locate and progress in the host.
Received: 27 June 1995 / Accepted: 13 November 1995 相似文献
108.
The development of a sensitive and specific enzyme immunoassay for GA3 is reported. This method was based on the use of peroxidase labelled GA3 and immobilized antibodies. In order to obtain a rapid immunoassay, several steps of purification were analyzed to show their necessity. Barley seed extracts were assayed at different steps of purification to exhibit the effect of extract components on the assay. It was demonstrated that HPLC had to be performed when a selective quantitation of GA3 was required. This assay allowed GA3 to be measured with reproducibility as its unmethylated form and the quantitation of GA3 in barley seeds with this enzyme immunoassay was correlated to a GC-MS method.Abbreviations GA3
gibberellin A3
- EIA
enzyme immunoassay
- DMF
dimethylformamide
- TEA
tri(n)ethylamine
- BSA
bovine serum albumin
- OVA
ovalbumine
- ECF
ethylchloroformate
- PB
phosphate buffer 相似文献
109.
Takaki Hiwasa Jun Ma Yoshimasa Ike Nobuhiko Katunuma Shigeru Sakiyama 《Cell biochemistry and function》1995,13(4):293-296
Degradation of cyclin B was effectively suppressed when cells were treated with ALLN (N-acetylleucylleucylnorleucinal) which inhibits proteasome, calpain and cysteine proteinase cathepsins. In order to examine which protease degrades cyclin B, the effect of a cathepsin inhibitor, cystatin α, was investigated. The cystatin α gene was inserted into an inducible expression vector, pMSG, and transfected into NIH3T3 mouse fibroblasts. The expression of cystatin α was induced effectively in the transfected cells after treatment with dexamethasone. Overexpression of cystatin α resulted in an increase of the amount of cyclin B, suggesting that cysteine proteinase cathepsins might be involved in the degradation of cyclin B. 相似文献
110.
Hyperimmune and high-titered polyclonal pneumococcal antisera, specific for cross-reactive types within groups, were produced in adult rabbits. Purified capsular polysaccharide was injected intravenously into adult rabbits. One week later, these rabbits were given multiple intravenous injections of formalin-inactivated pneumococci of the cross-reactive type by an established method. Each of the resultant antisera were specific for the cross-reactive type indicating that the previous injection of the polysaccharide had induced epitope-specific tolerance. This method was successful for production of antisera against pneumococcal types 6A, 6B, 9N, 9V, 19F and 19A. Polyclonal rabbit pneumococcal antisera have some advantages over murine monoclonal antibodies for serologic studies and this method should be applicable for producing type-specific antibodies to cross-reactive polysaccharides of clinical interest. Further, this method is simpler and generally produces higher titered monovalent (factor) reagents than absorbed antisera. 相似文献