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81.
E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators 总被引:12,自引:0,他引:12
Angus DC Birmingham MC Balk RA Scannon PJ Collins D Kruse JA Graham DR Dedhia HV Homann S MacIntyre N 《JAMA》2000,283(13):1723-1730
Context Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not. Objective To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis. Design A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses. Setting Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals. Patients Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection. Intervention Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552). Main Outcome Measures The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation. Results The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo. Conclusions Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted. 相似文献
82.
Gonzales AJ; Christensen JG; Preston RJ; Goldsworthy TL; Tlsty TD; Fox TR 《Carcinogenesis》1998,19(7):1173-1183
83.
Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats 总被引:4,自引:1,他引:4
Harris AJ; Shaddock JG; Manjanatha MG; Lisenbey JA; Casciano DA 《Carcinogenesis》1998,19(8):1451-1458
Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is
a contaminant of the human food supply, particularly in parts of Africa and
Asia. AFB1-induced changes in gene expression may play a part in the
development of the toxic, immunosuppressive and carcinogenic properties of
this fungal metabolite. An understanding of the-role of AFB1 in modulating
gene regulation should provide insight regarding mechanisms of AFB1-induced
carcinogenesis. We used three PCR- based subtractive techniques to identify
AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential
display PCR (DD-PCR), representational difference analysis (RDA) and
suppression subtractive hybridization (SSH). Each of the three techniques
identified AFB1- responsive genes, although no individual cDNA was isolated
by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH
were found to represent eight genes that are differentially expressed as a
result of AFB1 exposure. Genes whose mRNA levels were increased in cultured
primary rat hepatocytes after AFB1 treatment were corticosteroid binding
globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin,
C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase
Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels
after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When
liver RNA from AFB1-treated male F344 rats was evaluated for transferrin,
CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and
an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen.
Analysis of the potential function of these genes in maintaining cellular
homeostasis suggests that their differential expression could contribute to
the toxicity associated with AFB1 exposure.
相似文献
84.
Christen HJ Hanefeld F Kruse E Imhäuser S Ernst JP Finkenstaedt M 《Developmental medicine and child neurology》2000,42(2):122-132
Foix-Chavany-Marie syndrome (FCMS) is a distinct clinical picture of suprabulbar (pseudobulbar) palsy due to bilateral anterior opercular lesions. Symptoms include anarthria/severe dysarthria and loss of voluntary muscular functions of the face and tongue, and problems with mastication and swallowing with preservation of reflex and autonomic functions. FCMS may be congenital or acquired as well as persistent or intermittent. The aetiology is heterogeneous; vascular events in adulthood, nearly exclusively affecting adults who experience multiple subsequent strokes; CNS infections; bilateral dysgenesis of the perisylvian region; and epileptic disorders. Of the six cases reported here, three children had FCMS as the result of meningoencephalitis, two children had FCMS due to a congenital bilateral perisylvian syndrome, and one child had intermittent FCMS due to an atypical benign partial epilepsy with partial status epilepticus. The congenital dysgenetic type of FCMS and its functional epileptogenic variant share clinical and EEG features suggesting a common pathogenesis. Consequently, an increased vulnerability of the perisylvian region to adverse events in utero is discussed. In honour of Worster-Drought, who described the clinical entity in children 40 years ago, the term Worster-Drought syndrome is proposed for this unique disorder in children. 相似文献
85.
Jacob M. McLeod Charles O. Brantigan Kristen Alix Dustin L. Kruse Paul A. Stone 《The Journal of foot and ankle surgery》2013,52(3):383-388
Antiphospholipid syndrome is a hypercoagulable disease that can present foot and ankle surgeons with a unique challenge in treating patients who present with thrombosis and ischemia despite having normal pedal pulses. Appropriate perioperative management is imperative in these patients, because limb- and life-threatening complications can occur postoperatively, despite aggressive anticoagulation. We present the case of a 46-year-old male who underwent a transmetatarsal amputation and, despite aggressive therapy, developed a myriad of complications postoperatively. At 10 months postoperatively, the patient was doing well in an accommodative orthotic with minimal pain while receiving continued aggressive therapy and follow-up examinations by a number of specialists to treat his antiphospholipid syndrome. 相似文献
86.
87.
88.
James L. Cox Andrei Churyla S. Chris Malaisrie Jane Kruse Duc Thinh Pham Olga N. Kislitsina Patrick M. McCarthy 《The Canadian journal of cardiology》2018,34(11):1482-1491
The initial surgical attempts to treat atrial fibrillation (AF) were isolation procedures designed to confine the arrhythmia to a specific area of the heart for relief of symptoms. The first surgical attempt to ablate AF was unsuccessful but was quickly followed by the Maze-I procedure on September 25, 1987. Because of several adverse sequelae of the Maze-I procedure, it was sequentially modified to the Maze-II and then Maze-III procedures. The Maze-IV procedure was introduced some 10 years later; these are the only 4 procedures that adhere to the concept of a maze pattern of lesions to ablate AF and leave both atria capable of being activated during normal sinus rhythm. The term maze procedure has become generic for virtually any operation designed to treat AF, but procedures that do not adhere to the concept of creating lesions of conduction block in the pattern of a maze are not maze procedures. These include, among others, the Wolf Mini-Maze, the Left-Sided Maze, and the 5-Box Maze, none of which are truly based on the maze-pattern concept. The cardinal feature of maze procedures that is necessary for both effectiveness and comparability to classical maze procedures includes lines of conduction block that preclude macro-reentry anywhere in either atrium while leaving both atria capable of activation by a sinus-generated impulse. Components essential to achieving this include appropriate lesions in both atria, the absence of gaps that allow electrical activity to bypass an intended line of block, and the absence of alternate pathways by which impulses can reach the intended maze exit. 相似文献
89.
90.
Medora J. Huseby Andrew C. Kruse Jeff Digre Petra L. Kohler Jillian A. Vocke Ethan E. Mann Kenneth W. Bayles Gregory A. Bohach Patrick M. Schlievert Douglas H. Ohlendorf Cathleen A. Earhart 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(32):14407-14412
Biofilms are surface-associated communities of microbes encompassed by an extracellular matrix. It is estimated that 80% of all bacterial infections involve biofilm formation, but the structure and regulation of biofilms are incompletely understood. Extracellular DNA (eDNA) is a major structural component in many biofilms of the pathogenic bacterium Staphylococcus aureus, but its role is enigmatic. Here, we demonstrate that beta toxin, a neutral sphingomyelinase and a virulence factor of S. aureus, forms covalent cross-links to itself in the presence of DNA (we refer to this as biofilm ligase activity, independent of sphingomyelinase activity) producing an insoluble nucleoprotein matrix in vitro. Furthermore, we show that beta toxin strongly stimulates biofilm formation in vivo as demonstrated by a role in causation of infectious endocarditis in a rabbit model. Together, these results suggest that beta toxin cross-linking in the presence of eDNA assists in forming the skeletal framework upon which staphylococcal biofilms are established. 相似文献