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1.
2.
Ethinyl estradiol treats collagen-induced arthritis in DBA/1LacJ mice by inhibiting the production of TNF-alpha and IL-1beta 总被引:3,自引:0,他引:3
Subramanian S Tovey M Afentoulis M Krogstad A Vandenbark AA Offner H 《Clinical immunology (Orlando, Fla.)》2005,115(2):162-172
We previously demonstrated the therapeutic effects of ethinyl estradiol (EE), an orally active estrogen and a component of birth control pills, in encephalitogenic autoimmune encephalomyelitis (EAE). In this study, we report the effectiveness of EE in treating collagen-induced arthritis (CIA) induced with bovine type II collagen (bCII) in DBA/1LacJ mice, a CIA susceptible strain. Both low and high doses of EE notably suppressed clinical and histological signs of CIA in a dose-dependent manner compared to vehicle-treated controls. Oral treatment with EE decreased proliferation and secretion of pro-inflammatory factors, TNF-alpha IFN-gamma, MCP-1 and IL-6 by bCII peptide-specific T cells, production of bCII-specific IgG2a antibodies, and mRNA for cytokines, chemokines and chemokine receptors in joint tissue. This is the first report demonstrating effective treatment of joint inflammation and clinical signs of CIA with orally administered ethinyl estradiol, thus supporting its possible clinical use for treating rheumatoid arthritis in humans. 相似文献
3.
The ontogeny of the behavioral ability to compensate for sodium deficit was studied in the rat. The experiments showed that: (1) Before weaning age, sodium-depleted pups will increase their avidity for 3% NaCl solution; (2) the ability to select and drink a salt solution in response to a sodium deficit continues to evolve between 17–24 days of age, and that pups at these ages will modify their intake of salt and water as do adult rats when rectifiying plasma osmolality; (3) The increased appetite for sodium is evident even when depleted preweanlings are dehydrated and provided with solid NaCl tablets to lick, showing that sodium appetite and hydrational status are already dissociated at this age; and finally, (4) sodium depletion first induces an increase in intake of orally infused 3% NaCl solution in 12-day-old pups. The picture of the development of salt appetite in the suckling rat that these findings present is of a precocious competence to meet a challenge to sodium homeostasis. In this respect salt appetite emerges in parallel to the other ingestive behaviors © 1993 John Wiley & Sons, Inc. 相似文献
4.
Satoshi Fujita Hans C. Dreyer Micah J. Drummond Erin L. Glynn Jerson G. Cadenas Fumiaki Yoshizawa Elena Volpi Blake B. Rasmussen 《The Journal of physiology》2007,582(2):813-823
The mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) are important nutrient- and energy-sensing and signalling proteins in skeletal muscle. AMPK activation decreases muscle protein synthesis by inhibiting mTOR signalling to regulatory proteins associated with translation initiation and elongation. On the other hand, essential amino acids (leucine in particular) and insulin stimulate mTOR signalling and protein synthesis. We hypothesized that anabolic nutrients would be sensed by both AMPK and mTOR, resulting in an acute and potent stimulation of human skeletal muscle protein synthesis via enhanced translation initiation and elongation.
We measured muscle protein synthesis and mTOR-associated upstream and downstream signalling proteins in young male subjects ( n = 14) using stable isotopic and immunoblotting techniques. Following a first muscle biopsy, subjects in the 'Nutrition' group ingested a leucine-enriched essential amino acid–carbohydrate mixture (EAC). Subjects in the Control group did not consume nutrients. A second biopsy was obtained 1 h later. Ingestion of EAC significantly increased muscle protein synthesis, modestly reduced AMPK phosphorylation, and increased Akt/PKB (protein kinase B) and mTOR phosphorylation ( P < 0.05). mTOR signalling to its downstream effectors (S6 kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation status) was also increased ( P < 0.05). In addition, eukaryotic elongation factor 2 (eEF2) phosphorylation was significantly reduced ( P < 0.05). Protein synthesis and cell signalling (phosphorylation status) was unchanged in the control group ( P > 0.05).
We conclude that anabolic nutrients alter the phosphorylation status of both AMPK- and mTOR-associated signalling proteins in human muscle, in association with an increase in protein synthesis not only via enhanced translation initiation but also through signalling promoting translation elongation. 相似文献
We measured muscle protein synthesis and mTOR-associated upstream and downstream signalling proteins in young male subjects ( n = 14) using stable isotopic and immunoblotting techniques. Following a first muscle biopsy, subjects in the 'Nutrition' group ingested a leucine-enriched essential amino acid–carbohydrate mixture (EAC). Subjects in the Control group did not consume nutrients. A second biopsy was obtained 1 h later. Ingestion of EAC significantly increased muscle protein synthesis, modestly reduced AMPK phosphorylation, and increased Akt/PKB (protein kinase B) and mTOR phosphorylation ( P < 0.05). mTOR signalling to its downstream effectors (S6 kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation status) was also increased ( P < 0.05). In addition, eukaryotic elongation factor 2 (eEF2) phosphorylation was significantly reduced ( P < 0.05). Protein synthesis and cell signalling (phosphorylation status) was unchanged in the control group ( P > 0.05).
We conclude that anabolic nutrients alter the phosphorylation status of both AMPK- and mTOR-associated signalling proteins in human muscle, in association with an increase in protein synthesis not only via enhanced translation initiation but also through signalling promoting translation elongation. 相似文献
5.
Calcium is an essential nutrient, particularly during growth and during reproduction, and the latter is probably why the avidity for calcium may be greater in females of some species. However, in humans, despite widespread belief in calcium appetite, it has not been studied experimentally. Here we compared the hedonic responses of 17 men and 24 women to test whether women show a greater avidity for calcium in line with its greater biological significance for them. We find no gender difference in the hedonic response to calcium, and no change with the menstrual cycle. 相似文献
6.
Micah R. Chan 《Seminars in dialysis》2008,21(6):516-521
Despite aggressive efforts to increase autogenous fistula prevalence, catheters remain an essential access modality to a large percentage of the hemodialysis population. Central venous catheter dysfunction, which includes catheter‐related bacteremia and thrombotic occlusion, comprises the majority of complications which affect dialysis adequacy, patient quality of life, patient survival, and the economics of health care. This review provides a comprehensive overview of hemodialysis central venous catheter dysfunction, its epidemiology and risk factors, and avenues of prevention and treatment. Novel directions for future investigation are also addressed. 相似文献
7.
Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK/IKK alpha-dependent noncanonical NF-kappaB activation 总被引:1,自引:0,他引:1 下载免费PDF全文
Luftig M Yasui T Soni V Kang MS Jacobson N Cahir-McFarland E Seed B Kieff E 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(1):141-146
Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1)-induced NF-kappaB activation is important for infected cell survival. LMP1 activates NF-kappaB, in part, by engaging tumor necrosis factor (TNF) receptor-associated factors (TRAFs), which also mediate NF-kappaB activation from LTbetaR and CD40. LTbetaR and CD40 activation of p100/NF-kappaB2 is now known to be NIK/IKKalpha-dependent and IKKbeta/IKKgamma independent. In the experiments described here, we found that EBV LMP1 induced p100/NF-kappaB2 processing in human lymphoblasts and HEK293 cells. LMP1-induced p100 processing was NIK/IKKalpha dependent and IKKbeta/IKKgamma independent. Furthermore, the LMP1 TRAF-binding site was required for p100 processing and p52 nuclear localization, whereas the LMP1 death domain-binding site was not. Moreover, the LMP1 TRAF-binding site preferentially caused RelB nuclear accumulation. In murine embryo fibroblasts (MEFs), IKKbeta was essential for LMP1 up-regulation of macrophage inflammatory protein (MIP)-2, TNFalpha, I-TAC, ELC, MIG, and CXCR4 RNAs. Interestingly, in IKKalpha knockout MEFs, LMP1 hyperinduced MIP-2, TNFalpha, and I-TAC expression, consistent with a role for IKKalpha in down-modulating canonical IKKbeta activation or its effects. In contrast, LMP1 failed to up-regulate CXCR4 and MIG RNA in IKKalpha knockout MEFs, indicating a dependence on noncanonical IKKalpha activation. Furthermore, LMP1 up-regulation of MIP-2 RNA in MEFs was both IKKbeta- and IKKgamma-dependent, whereas LMP1 upregulation of MIG and I-TAC RNA was fully IKKgamma independent. Thus, LMP1 induces typical canonical IKKbeta/IKKgamma-dependent, atypical canonical IKKbeta-dependent/IKKgamma-independent, and noncanonical NIK/IKKalpha-dependent NF-kappaB activations; NIK/IKKalpha-dependent NF-kappaB activation is principally mediated by the LMP1 TRAF-binding site. 相似文献
8.
Effect of Matrix Metalloproteinase Inhibition by Doxycycline on Myocardial Healing and Remodeling after Myocardial Infarction 总被引:2,自引:0,他引:2
Tessone A Feinberg MS Barbash IM Reich R Holbova R Richmann M Mardor Y Leor J 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2005,19(6):383-390
Summary The aim of conducting this study was to assess the clinical relevance of matrix metalloproteinase (MMP) inhibition by doxycycline,
an effective MMP inhibitor, in a rat model of extensive myocardial infarction (MI) and left ventricular (LV) dysfunction.
Rats (n = 22) were subjected to extensive anterior MI. Doxycycline (25 mg SC, daily) or saline (control) injections were started
for nine days thereafter. The effect of doxycycline on MMP activity in the infarcted and remote myocardium was measured by
zymography, in another subgroup (n = 8), nine days after MI. Echocardiography and magnetic resonance imaging (MRI) studies were performed at one and thirty
days after MI to assess LV remodeling and function. After 4 weeks, hearts were fixed, and subjected to morphometric and histological
analysis. Compared with control, doxycycline treatment attenuated MMP-9 and -2 activity in both infarcted and remote myocardium.
Serial echocardiography studies showed that doxycycline failed to attenuate scar thinning, LV dilatation and dysfunction.
MRI study showed that doxycycline impaired LV compensatory hypertrophy. Furthermore, compared with control, doxycycline reduced
vessel density (/mm2 ± SEM) in the infarcted myocardium (84 ± 16 vs. 46 ± 9/mm2, respectively; p < 0.05).
Our work suggest that effective MMPs’ inhibition in the infarcted and remote myocardium by doxycycline does not prevent LV
remodeling and dysfunction but impairs angiogenesis and compensatory LV hypertrophy. Our findings caution against aggressive,
non-selective inhibition of MMPs in the early healing phase after MI. 相似文献
9.
10.
Joel E. Rosenberg Alexander S. Yevzlin Micah R. Chan Amanda M. Valliant Brad C. Astor 《Seminars in dialysis》2015,28(5):544-547
Physical examination (PE) is an excellent means of predicting arteriovenous fistula (AVF) dysfunction. Although quick and inexpensive, PE is seldom used as a tool to assess stenosis by general nephrologists, dialysis nurses, and dialysis technicians. Previous studies have demonstrated that PE can be taught to interventional specialists, but the perception remains that it is too complex to be performed by other health care professionals. We hypothesized that the physical exam can be taught to a nonmedical professional, and that, with time, it would be comparable to the physical exam performed by a full‐time interventional specialist. An undergraduate student and an interventional specialist (MD) examined AVF for dysfunction in a tertiary care hospital over a 6‐month period. PE was performed on patients who were suspected of having dialysis access dysfunction and were referred for angiography and intervention (n = 49). Physical exam findings were categorized blindly by each examiner into four categories of lesion location: inflow, outflow, both, or neither. Data were privately recorded and compared to the gold standard of angiographic results. Potential confounding variables, including age, gender, diabetic status, and location of AVF were recorded. Weighted Cohen's kappa value was used as a measurement of the level of agreement beyond chance between the diagnoses made by physical exam and angiography. The full‐time interventional specialist demonstrated correct prediction of lesion location of 89.8% (kappa = 0.850), while the undergraduate student had a correct prediction of 77.6% (kappa = 0.625). The student's performance, however, differed significantly over time. The student correctly predicted the location of the lesion in 6 (42.9%) of the first 14 patients (kappa = 0.082), compared to 32 (91.4%) of the last 35 patients (kappa = 0.855). We suggest that physical exam of AVF can be taught to a nonmedical professional in a short duration of time and the predictive value of the exam can be similar to that of an interventional specialist. 相似文献