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991.
Emilie Ramberg Maria Olausson Tem Bendix Salkvist Jørgensen Malene Lindholmer Nepper Priya Bhardwaj Tomas Sorm Binko Jan Roland Petersen Gitte Gleerup Fornitz 《The American journal of emergency medicine》2017,35(1):136-143
Aims
Assessment of right ventricular (RV) function in acute pulmonary embolism (PE) has prognostic significance. The aim of this study was to evaluate right atrium (RA) and RV myocardial damage with 2-dimensional speckle-tracking in patients with an acute central vs an acute peripheral PE.Methods and Results
Twenty-six patients with acute PE and 10 controls were retrospectively enrolled. Right atrium and RV myocardial deformation was analyzed using speckle-tracking imaging echocardiography. Parameters were evaluated to illustrate myocardial damage in patients with a central or a peripherally located PE.Thirteen of the enrolled patients had a massive central PE, and thirteen subjects had a peripheral located PE. Baseline characteristics were not significantly different between the 3 groups besides a more elevated heart rate among patients with a central PE (P = .02) and a tendency of an increased D-dimer in this group. Right ventricular dimensions were more affected among patients with a PE. Compared with controls, segmental RV and RA strain/strain rate in the free wall was significantly reduced in patients with PE (P < .05). No difference was shown between the 2 groups of PE.Conclusion
This pilot study suggests that basal-/mid-segments of RA and RV free wall are more affected in patients with a PE compared with controls. Interestingly, we found no significant difference in myocardial RA and RV damage between patients with a central and a peripheral PE. We advocate that PE no matter central or peripheral is a serious condition and that a peripheral PE has to be intensively treated similar to a central PE. 相似文献992.
Effect of aqueous extract and anthocyanins of calyces of Hibiscus sabdariffa (Malvaceae) in rats with adenine‐induced chronic kidney disease 下载免费PDF全文
993.
Bolind PK Johansson CB Becker W Langer L Sevetz EB Albrektsson TO 《Clinical oral implants research》2005,16(4):447-455
Objectives: In the light microscope compare the amount of bone saucerization for non‐threaded cylindrical and threaded implant designs in retrieved samples from patients. Material and method: Consecutively received retrieved oral implants from 117 patients, whereof 85 non‐threaded cylindrical and 85 Brånemark implants, have been included in the study. For 75 non‐threaded cylindrical and 46 Brånemark implants was the entire implant length available for calculation. Undecalcified ground sections were investigated in the light microscope with calculation of percentage of implant length coronal to the first bone–implant contact and percentage of bone to implant contact. Results: Mean value for implant length coronal to first bone–implant contact was 65%, standard error of the mean (SEM) 3 (range 0–100%), for non‐threaded cylindrical implants and 43%, SEM 6 (range 0–100%) for Brånemark implants. Mean values of bone contact along the entire implant length was 23%, SEM 2 (range 0–65%), for the non‐threaded cylindrical implants and 33%, SEM 5 (range 0–93%) for the Brånemark implants. Conclusion: Within the limitations of this retrospective, retrieval study non‐threaded cylindrical implants demonstrated a greater bone saucerization when evaluated in the light microscope. 相似文献
994.
Hyperthermia adds to trabectedin effectiveness and thermal enhancement is associated with BRCA2 degradation and impairment of DNA homologous recombination repair 下载免费PDF全文
Kirsten Lauber Roman Hennel Ana Sofia Cardoso Martins Yang Guo Claus Belka Simone Mörtl Eike Gallmeier Roland Kanaar Ulrich Mansmann Tomas Hucl Lars H. Lindner Wolfgang Hiddemann Rolf D. Issels 《International journal of cancer. Journal international du cancer》2016,139(2):467-479
The tetrahydroisoquinoline trabectedin is a marine compound with approved activity against human soft‐tissue sarcoma. It exerts antiproliferative activity mainly by specific binding to the DNA and inducing DNA double‐strand breaks (DSB). As homologous recombination repair (HRR)‐deficient tumors are more susceptible to trabectedin, hyperthermia‐mediated on‐demand induction of HRR deficiency represents a novel and promising strategy to boost trabectedin treatment. For the first time, we demonstrate enhancement of trabectedin effectiveness in human sarcoma cell lines by heat and characterize cellular events and molecular mechanisms related to heat‐induced effects. Hyperthermic temperatures (41.8 or 43°C) enhanced significantly trabectedin‐related clonogenic cell death and G2/M cell cycle arrest followed by cell type‐dependent induction of apoptosis or senescence. Heat combination increased accumulation of γH2AX foci as key marker of DSBs. Expression of BRCA2 protein, an integral protein of the HRR machinery, was significantly decreased by heat. Consequently, recruitment of downstream RAD51 to γH2AX‐positive repair foci was almost abolished indicating relevant impairment of HRR by heat. Accordingly, enhancement of trabectedin effectiveness was significantly augmented in BRCA2‐proficient cells by hyperthermia and alleviated in BRCA2 knockout or siRNA‐transfected BRCA2 knockdown cells. In peripheral blood mononuclear cells isolated from sarcoma patients, increased numbers of nuclear γH2AX foci were detected after systemic treatment with trabectedin and hyperthermia of the tumor region. The findings establish BRCA2 degradation by heat as a key factor for a novel treatment strategy that allows targeted chemosensitization to trabectedin and other DNA damaging antitumor drugs by on‐demand induction of HRR deficiency. 相似文献
995.
Beta2 integrin phosphorylation on Thr758 acts as a molecular switch to regulate 14-3-3 and filamin binding 下载免费PDF全文
Takala H Nurminen E Nurmi SM Aatonen M Strandin T Takatalo M Kiema T Gahmberg CG Ylänne J Fagerholm SC 《Blood》2008,112(5):1853-1862
Leukocyte integrins of the beta2 family are essential for immune cell-cell adhesion. In activated cells, beta2 integrins are phosphorylated on the cytoplasmic Thr758, leading to 14-3-3 protein recruitment to the beta2 integrin. The mutation of this phosphorylation site impairs cell adhesion, actin reorganization, and cell spreading. Thr758 is contained in a Thr triplet of beta2 that also mediates binding to filamin. Here, we investigated the binding of filamin, talin, and 14-3-3 proteins to phosphorylated and unphosphorylated beta2 integrins by biochemical methods and x-ray crystallography. 14-3-3 proteins bound only to the phosphorylated integrin cytoplasmic peptide, with a high affinity (K(d), 261 nM), whereas filamin bound only the unphosphorylated integrin cytoplasmic peptide (K(d), 0.5 mM). Phosphorylation did not regulate talin binding to beta2 directly, but 14-3-3 was able to outcompete talin for the binding to phosphorylated beta2 integrin. X-ray crystallographic data clearly explained how phosphorylation eliminated filamin binding and induced 14-3-3 protein binding. Filamin knockdown in T cells led to an increase in stimulated cell adhesion to ICAM-1-coated surfaces. Our results suggest that the phosphorylation of beta2 integrins on Thr758 acts as a molecular switch to inhibit filamin binding and allow 14-3-3 protein binding to the integrin cytoplasmic domain, thereby modulating T-cell adhesion. 相似文献
996.
Jaques F Jousset H Tomas A Prost AL Wollheim CB Irminger JC Demaurex N Halban PA 《Endocrinology》2008,149(5):2494-2505
Cell-to-cell interactions play an important role in insulin secretion. Compared with intact islets, dispersed pancreatic beta-cells show increased basal and decreased glucose-stimulated insulin secretion. In this study, we used mouse MIN6B1 cells to investigate the mechanisms that control insulin secretion when cells are in contact with each other or not. RNAi-mediated silencing of the adhesion molecule E-cadherin in confluent cells reduced glucose-stimulated secretion to the levels observed in isolated cells but had no impact on basal secretion. Dispersed cells presented high cytosolic Ca(2+) activity, depolymerized cytoskeleton and ERK1/2 activation in low glucose conditions. Both the increased basal secretion and the spontaneous Ca(2+) activity were corrected by transient removal of Ca(2+) or prolonged incubation of cells in low glucose, a procedure that restored the ability of dispersed cells to respond to glucose (11-fold stimulation). In conclusion, we show that dispersed pancreatic beta-cells can respond robustly to glucose once their elevated basal secretion has been corrected. The increased basal insulin secretion of dispersed cells is due to spontaneous Ca(2+) transients that activate downstream Ca(2+) effectors, whereas engagement of cell adhesion molecules including E-cadherin contributes to the greater secretory response to glucose seen in cells with normal intercellular contacts. 相似文献
997.
Dreborg S Sundström G Larsson TA Larhammar D 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(40):15487-15492
The opioid peptides and receptors have prominent roles in pain transmission and reward mechanisms in mammals. The evolution of the opioid receptors has so far been little studied, with only a few reports on species other than tetrapods. We have investigated species representing a broader range of vertebrates and found that the four opioid receptor types (delta, kappa, mu, and NOP) are present in most of the species. The gene relationships were deduced by using both phylogenetic analyses and chromosomal location relative to 20 neighboring gene families in databases of assembled genomes. The combined results show that the vertebrate opioid receptor gene family arose by quadruplication of a large chromosomal block containing at least 14 other gene families. The quadruplication seems to coincide with, and, therefore, probably resulted from, the two proposed genome duplications in early vertebrate evolution. We conclude that the quartet of opioid receptors was already present at the origin of jawed vertebrates approximately 450 million years ago. A few additional opioid receptor gene duplications have occurred in bony fishes. Interestingly, the ancestral receptor gene duplications coincide with the origin of the four opioid peptide precursor genes. Thus, the complete vertebrate opioid system was already established in the first jawed vertebrates. 相似文献
998.
999.
1000.
Therapeutic use of nicergoline 总被引:1,自引:0,他引:1
Winblad B Fioravanti M Dolezal T Logina I Milanov IG Popescu DC Solomon A 《Clinical drug investigation》2008,28(9):533-552
The ergot alkaloid derivative nicergoline became clinically available about 35 years ago in the 1970s. Nicergoline has a broad spectrum of action: (i) as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Acting on several basic pathophysiological mechanisms, nicergoline has therapeutic potential in a number of disorders. This article provides an overview of the published clinical evidence relating to the efficacy and safety of nicergoline (30 mg twice daily) in the treatment of dementia (including Alzheimer's disease and vascular dementia) and vascular and balance disorders. For dementia of different aetiologies, the therapeutic benefit of nicergoline has been established, with up to 89% of patients showing improvements in cognition and behaviour. After as little as 2 months of treatment, symptom improvement is apparent compared with placebo, and most patients are still improved or stable after 12 months. Concomitant neurophysiological changes in the brain indicate (after only 4-8 weeks' treatment) improved vigilance and information processing. In patients with balance disorders, mean improvements of 44-78% in symptom severity and quality of life have been observed with nicergoline. Although clinical experience with nicergoline in vascular disorders is limited to relatively short-term, small-scale studies, it has been successfully used in rehabilitation therapy of patients with chronic ischaemic stroke. Open-label evaluations suggest that nicergoline may also be valuable in glaucoma, depression and peripheral arterio-pathy. Adverse events of nicergoline, if any, are related to the central nervous system, the metabolic system and the overall body. Most are considered typical symptoms of ergot derivatives. Because of their generally mild and transient nature, treatment discontinuations occur relatively infrequently. The efficacy of nicergoline combined with a favourable safety and tolerability profile at commonly applied doses (60 mg/day) make this agent a valuable therapy in patients with mild to moderate dementia, vascular diseases and balance disorders. 相似文献