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Lee L. Eckhardt MD Amanda L. Farley MS Esther Rodriguez MD Karen Ruwaldt BS Daniel Hammill David J. Tester BS Michael J. Ackerman MD PhD Jonathan C. Makielski MD 《Heart rhythm》2007,4(3):323-329
BACKGROUND: Loss-of-function mutations in the KCNJ2 cause approximately 50% of Andersen-Tawil Syndrome (ATS) characterized by a classic triad of periodic paralysis, ventricular arrhythmia, and dysmorphic features. Do KCNJ2 mutations occur in patients lacking this triad and lacking a family history of ATS? OBJECTIVES: The purpose of this study was to identify and characterize mutations in the KCNJ2-encoded inward rectifier potassium channel Kir2.1 from patients referred for genetic arrhythmia testing. METHODS: Mutational analysis of KCNJ2 was performed for 541 unrelated patients. The mutations were made in wild type (WT) and expressed in COS-1 cells and voltage clamped for ion currents. RESULTS: Three novel missense mutations (R67Q, R85W, and T305A) and one known mutation (T75M) were identified in 4/249 (1.6%) patients genotype-negative for other known arrhythmia genes with overall incidence 4/541 (0.74%). They had prominent U-waves, marked ventricular ectopy, and polymorphic ventricular tachycardia but no facial/skeletal abnormalities. Periodic paralysis was present in only one case. Outward current was decreased to less than 5% of WT for all mutants expressed alone. Co-expression with WT (simulating heterozygosity) caused a marked dominant negative effect for T75M and R82W, no dominant negative effect for R67Q, and a novel selective enhancement of inward rectification for T305A. CONCLUSIONS: KCNJ2 loss of function mutations were found in approximately 1% of patients referred for genetic arrhythmia testing that lacked criteria for ATS. Characterization of three new mutations identified a novel dominant negative effect selectively reducing outward current for T305A. These results extend the range of clinical phenotype and molecular phenotype associated with KCNJ2 mutations. 相似文献
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Peter Rasmussen Ellen A Dawson Lars Nybo Johannes J van Lieshout Niels H Secher Albert Gjedde 《Journal of cerebral blood flow and metabolism》2007,27(5):1082-1093
Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78%+/-4%; mean+/-s.d.) was halfway between the arterial (98%+/-1%) and jugular venous oxygenation (SvO2; 61%+/-6%). Both NIRS devices monitored SCap (P<0.001) within approximately 5% as SvO2 increased from 39%+/-5% to 79%+/-7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29+/-8 to 65+/-15 cm/sec. When SCap fell below approximately 70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P<0.001) and brain lactate release increased concomitantly (P<0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r>0.74; P<0.05). These results show that NIRS is an adequate cerebral capillary-oxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal. 相似文献
55.
Psychosocial factors at work and perceived health among agricultural meat industry workers in France
Christine Cohidon Patrick Morisseau Francis Derriennic Marcel Goldberg Ellen Imbernon 《International archives of occupational and environmental health》2009,82(7):807-818
Objective The objective of this study was to describe the perceived health status of the meat industry employees—i.e., working in the
slaughtering, cutting, and boning of large animals and poultry—and its relation to their organisational and psychosocial constraints
at work.
Methods This postal survey included all 3,000 employees of the meat industry (beef, pork and poultry) in four districts in Brittany,
France, whose companies were affiliated with the agricultural branch of the national health insurance fund. The questionnaire
asked for social and demographic data and information describing their job and the organisation of their work. The psychosocial
factors at work were described according to Karasek’s questionnaire (demand, latitude and social support at work). Perceived
health was measured with the Nottingham Health Profile perceived health indicator.
Results This study shows the high prevalence of poor health reported by the workers in this industry. This poor perceived health was
worse in women and increased regularly with age. Among the psychosocial factors studied, high quantitative and qualitative
demand at work, inadequate resources for good work and to a lesser extent, inadequate prospects for promotion appear especially
associated with poor perceived health. Other factors often associated with poor perceived health included young age at the
first job and work hours that disrupt sleep rhythms (especially for women).
Conclusion Our results show that this population of workers is especially vulnerable from the point of view of perceived physical and
psychological health and is exposed to strong physical, organisational and psychosocial constraints at work. They also demonstrate
that poor perceived health is associated with some psychosocial (such as high psychological demand and insufficient resources)
and organisational factors at work. These results, in conjunction with those from other disciplines involved in studying this
industry, may help the companies to develop preventive activities. 相似文献
56.
Yngve Kvinnsland Trond Stokke Ellen Aurlien 《Journal of nuclear medicine》2007,48(2):327; author reply 327-327; author reply 328
57.
Yaotang Wu Guangping Dai Jerome L Ackerman Mirko I Hrovat Melvin J Glimcher Brian D Snyder Ara Nazarian David A Chesler 《Magnetic resonance in medicine》2007,57(3):554-567
Investigators often study rats by microCT to investigate the pathogenesis and treatment of skeletal disorders in humans. However, microCT measurements provide information only on bone mineral content and not the solid matrix. CT scans are often carried out on cancellous bone, which contains a significant volume of marrow cells, stroma, water, and fat, and thus the apparent bone mineral density (BMD) does not reflect the mineral density within the matrix, where the mineral crystals are localized. Water- and fat-suppressed solid-state proton projection imaging (WASPI) was utilized in this study to image the solid matrix content (collagen, tightly bound water, and other immobile molecules) of rat femur specimens, and meet the challenges of small sample size and demanding submillimeter resolution. A method is introduced to recover the central region of k-space, which is always lost in the receiver dead time when free induction decays (FIDs) are acquired. With this approach, points near the k-space origin are sampled under a small number of radial projections at reduced gradient strength. The typical scan time for the current WASPI experiments was 2 hr. Proton solid-matrix images of rat femurs with 0.4-mm resolution and 12-mm field of view (FOV) were obtained. This method provides a noninvasive means of studying bone matrix in small animals. 相似文献
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