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81.
3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of Flu-HPA on the ability of purified alpha 2-antiplasmin to inhibit purified plasmin was studied. Plasmin activity was determined using 125I-fibrin plates or the spectrophotometric tripeptide substrate, Val-Leu-Lys-paranitroanilide. At Flu-HPA concentrations greater than 1 mM, the inhibitory activity of alpha 2-antiplasmin was abolished in a time-dependent and concentration- dependent manner. The influence of Flu-HPA on the ability of purified Cl inhibitor to inhibit purified plasma kallikrein and beta-Factor XIIa was also studied. Cl inhibitor activity was abolished by Flu-HPA at concentrations greater than 2 mM. Notably, Flu-HPA up to 60 mM did not affect the amidolytic activities of plasmin, kallikrein, or beta-Factor XIIa. Flu-HPA did not release enzyme activity from preformed complexes of either alpha 2-antiplasmin and plasmin of Cl inhibitor and kallikrein. A water-soluble derivative of flufenamic acid, N-flufenamyl- glutamic acid, also inactivated alpha 2-antiplasm and Cl inhibitor. This inactivation was shown to be reversible. These results indicate that synthetic fibrinolytic compounds such as flufenamic acid derivatives may promote fibrinolysis by directly inactivating alpha 2- antiplasmin and Cl inhibitor. 相似文献
82.
Toby A. Eyre Lindsey E. Roeker Christopher P. Fox Satyen H. Gohill Renata Walewska Harriet S. Walter Francesco Forconi Angus Broom Arvind Arumainathan Danielle M. Brander John N. Allan Stephen J. Schuster Brian T. Hill Frederick Lansigan Bruce D. Cheson Nicole Lamanna Catherine C. Coombs Paul M. Barr Alan P. Skarbnik Mazyar Shadman Chaitra S. Ujjani Laurie Pearson John M. Pagel Ryan Jacobs Anthony R. Mato 《British journal of haematology》2020,188(6):918-923
Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton's tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and <75 years treated in the relapsed, refractory non-trial setting. We demonstrate that venetoclax has equivalent efficacy and safety in relapsed/refractory CLL patients who are elderly, the majority of whom are previous ibrutinib-exposed and therefore may otherwise have few clear therapeutic options. 相似文献
83.
Peter Coombs Sarah L. Walton Devaki Maduwegedera Rebecca L. Flower Kate M. Denton 《Anatomical record (Hoboken, N.J. : 2007)》2020,303(10):2646-2656
Obtaining growth and physiologic data in the postnatal laboratory animal is common. However, monitoring growth in utero is far more difficult, with little data available except upon termination of pregnancy. High-resolution ultrasound was used to monitor growth, morphology, and fetal well-being in normotensive and hypertensive rabbits (21 fetuses) at day 16, 20, and 26 of the 32 day gestational period. Set protocols, comparable to those routinely assessed in humans, were devised and followed for each examination. Birth weight was greater in offspring of hypertensive as compared to normotensive mothers (p < 0.001); however, litter size was reduced. The greater birth weight was reflected in growth parameters measured throughout gestation indicating the predictive value of ultrasound. High-resolution ultrasound was a reliable and sensitive method for biometric and morphologic assessment of the fetal rabbit, demonstrating that growth trajectory of offspring of hypertensive mothers may be altered early in gestation. 相似文献
84.
Genetic and Molecular Predictors of High Vancomycin MIC in Staphylococcus aureus Bacteremia Isolates
Natasha E. Holmes John D. Turnidge Wendy J. Munckhof J. Owen Robinson Tony M. Korman Matthew V. N. O'Sullivan Tara L. Anderson Sally A. Roberts Sanchia J. C. Warren Geoffrey W. Coombs Hui-Leen Tan Wei Gao Paul D. R. Johnson Benjamin P. Howden 《Journal of clinical microbiology》2014,52(9):3384-3393
An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes. 相似文献
85.
Background
The kallikrein-kinin system (KKS) is an endogenous pathway involved in angiogenesis and tumourigenesis, both vital for cancer growth and progression.Objectives
To investigate the effect of two bradykinin receptor (B1R and B2R) agonists on growth and motility of prostate tumour (DU145) and micro-vascular endothelial cells (dMVECs).Methods
Increasing concentrations of selective B1R and B2R agonists were added to cultured cells. Cell proliferation and migration were assessed using the 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and modified Boyden Chamber assays, respectively. Where significant stimulation was found, the influence of an antagonist was also investigated.Results
Neither growth nor motility of endothelial cells was affected by either agonist. In DU145 cells, while the B2R agonist was without any significant effect, the B1R agonist stimulated proliferation and migration at concentrations of 10nM and 50nM respectively. Further, this effect was abrogated when cells were pre-incubated with a B1R antagonist.Conclusions
Unlike the physiologically-active B2R, the pathologically-inducible B1R may be implicated in prostate tumourigenic events. The involvement of the KKS in malignant prostate pathology supports on-going exploration of bradykinin receptor antagonists as target candidates in the development of alternate approaches to cancer therapy. 相似文献86.
KH Neppelenbroek RS Seó VM Urban S Silva LN Dovigo JH Jorge NH Campanha 《Oral diseases》2014,20(4):329-344
In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species. 相似文献
87.
Coronary arteriography performed by a physician assistant 总被引:1,自引:0,他引:1
Funding constraints and an oversupply of cardiologists mitigate against continued training of increasing numbers of cardiology fellows. In some institutions, the workload of the catheterization laboratory is an overriding factor. The ability of a physician assistant to perform some of this work was tested to determine if the number of fellows and the content of the fellowship training program could be uncoupled from the catheterization laboratory workload. Among the first 150 patients in whom coronary arteriography was performed by a physician assistant, no patient died or had a myocardial infarction or stroke. Two patients (1.3%) had minor complications: a retinal embolus and an infected puncture site. The complication rate in 150 consecutive cases performed by fellows was also 1.3%, a small myocardial infarction and a transient ischemic attack. Procedure times for the physician assistant and for the fellows were 41 +/- 13 and 44 +/- 18 minutes for preoperative patients and 62 +/- 24 and 70 +/- 20 minutes for postoperative patients. Corresponding fluoroscopy times were 11 +/- 5 and 12 +/- 7 minutes for the preoperative and 22 +/- 12 and 20 +/- 6 for postoperative patients. Only preoperative fluoroscopy times were statistically different (p = 0.02). Thus, substituting a physician assistant for a fellow to perform coronary arteriography is an option in institutions at which the number of studies exceeds the training needs of fellows. 相似文献
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