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41.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
42.
K S Kamel J H Ethier B J Stinebaugh F X Schloeder M L Halperin 《Kidney international》1990,38(3):507-511
When a large inorganic acid load is ingested by normals, the proton load is eliminated because the rate of excretion of ammonium can rise to 200 to 300 mmol/day. In subjects with ketoacidosis of chronic fasting, such a large increase in the rate of excretion of ammonium might not be possible because of ATP balance considerations in proximal cells. Subjects with ketoacidosis of chronic fasting excreted less net acid as defined in the conventional way when they consumed a large inorganic acid load (136 +/- 6 vs. 176 +/- 26 mmol/day in control fasted subjects). Nevertheless, the vast majority of this inorganic acid load was eliminated because they were in steady state and had only a slightly lower concentration of bicarbonate (13 +/- 0.6 vs. 15 +/- 0.5 mmol/liter) and ketoacid anions (3.3 +/- 0.2 vs. 5.5 +/- 0.2 mmol/liter) in their blood. Using a definition of net acid excretion where the component of bicarbonate loss was expanded to include "potential bicarbonate" (ketoacid anions) in the urine, the rate of excretion of net acid was higher in subjects who ingested the inorganic acid load, owing to a much lower rate of excretion of ketoacid anions (9 +/- 2 vs. 120 +/- 7 mmol/day). This lower rate of excretion was not only due to a lower filtered load, but also to a higher fractional reabsorption of ketoacid anions during acidosis (97 +/- 0.1 vs. 77 +/- 0.2%). This higher fractional reabsorption could not be explained by a lower filtered load of ketoacid anions or to a restricted intake of sodium.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
43.
Halperin W 《The Journal of ambulatory care management》1994,17(2):62-67
The prevention of occupational disease and injury requires focusing on the spectrum of services that would effectively contribute to prevention as well as the quality of constituent services. The broadest spectrum of services includes primary, secondary, and tertiary prevention and requires a team of professionals from medicine, nursing, industrial hygiene, and safety engineering. There are impediments to ensuring both the quality of care provided by individual professions and access to a broad array of services. Ensuring quality may be more dependent upon the spectrum of services utilized than in the variability of quality of any provider of care. 相似文献
44.
Mortality study of workers in 1,3-butadiene production units identified from a chemical workers cohort. 总被引:5,自引:1,他引:4
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E M Ward J M Fajen A M Ruder R A Rinsky W E Halperin C A Fessler-Flesch 《Environmental health perspectives》1995,103(6):598-603
The International Agency for Research on Cancer has given the designations of "sufficient evidence" of carcinogenicity of 1,3-butadiene in experimental animals and "limited evidence" of carcinogenicity in humans. To investigate the carcinogenic effect in humans, we conducted a cohort mortality study among 364 men who were assigned to any of three 1,3-butadiene production units located within several chemical plants in the Kanawha Valley of West Virginia, including 277 men employed in a U.S. Rubber Reserve Plant which operated during World War II. The butadiene production units included in this study were selected from an index developed by the Union Carbide Corporation, which listed for each chemical production unit within their South Charleston, West Virginia and Institute, West Virginia, plants all products, by-products, and reactants. Departments included in the study were those where butadiene was a primary product and neither benzene nor ethylene oxide was present. A total of 185 deaths were observed; the standardized mortality ratio (SMR) for all causes of death was 91, reflecting lower mortality among the study population than the U.S. population. The study found a significantly elevated standardized mortality ratio (SMR) for lymphosarcoma and reticulosarcoma based on four observed cases (SMR = 577; 95% CI = 157-1480), which persisted in an analysis using county referent rates. An excess of lymphosarcoma and reticulosarcoma among all workers and among workers with routine exposure to 1,3-butadiene was also observed in the only other cohort of 1,3-butadiene production workers previously studied.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells. 相似文献
49.
Importance of timing of risk factors for cerebral oedema during therapy for diabetic ketoacidosis. 总被引:4,自引:0,他引:4
Cerebral oedema is the most common cause of mortality and morbidity during the first day of conventional treatment for diabetic ketoacidosis in paediatric patients. It is possible that therapy contributes to its development. Risk factors that predispose to cerebral oedema should lead to an expansion of the intracellular and/or the extracellular fluid compartment(s) of the brain because water normally accounts for close to 80% of brain weight. With respect to the intracellular fluid compartment, the driving force to cause cell swelling is a gain of effective osmoles in brain cells and/or a significant decline in the effective osmolality of the extracellular fluid compartment. Factors leading to an expansion of the intracerebral extracellular fluid volume can be predicted from Starling forces acting at the blood-brain barrier. Some of these risk factors have an early impact, while others have their major effects later during therapy for diabetic ketoacidosis. Based on a theoretical analysis, suggestions to modify current therapy for diabetic ketoacidosis in children are provided. 相似文献
50.
Linear lesions in myocardium created by Nd:YAG laser using diffusing optical fibers: in vitro and in vivo results 总被引:3,自引:0,他引:3
Fried NM Lardo AC Berger RD Calkins H Halperin HR 《Lasers in surgery and medicine》2000,27(4):295-304
BACKGROUND AND OBJECTIVE: Linear lesions may be necessary for successful catheter ablation of cardiac arrhythmias such as atrial fibrillation. This study uses laser energy delivered through diffusing optical fibers as an alternative to radiofrequency energy for the creation of linear lesions in cardiac tissue in a single application. STUDY DESIGN/MATERIALS AND METHODS: Samples of canine myocardium were placed in a heated, circulating saline bath and irradiated with a 1.06-microm, continuous-wave Nd:YAG laser during in vitro studies. Laser ablation was then performed in vivo on the epicardial surface of the right ventricle during an open-chest procedure by using similar ablation parameters. Laser energy was delivered to the tissue by being diffused radially through flexible optical fiber tips oriented parallel to the tissue surface. Histology and temperature measurements verified transmurality, continuity, and linearity of the lesions. RESULTS: Peak tissue temperatures measured in vitro remained low (51 +/- 1 degrees C at the endocardial surface, 61 +/- 6 degrees C in the mid-myocardium, and 55 +/- 6 degrees C at the epicardial surface) with no evidence of tissue charring or vaporization. Lesion dimensions produced in vitro and in vivo were similar (depth, 6 mm; width, 8-10 mm; length, 16-22 mm), demonstrating that tissue perfusion in vivo did not significantly alter the heating. CONCLUSION: Long linear lesions, necessary for duplication of the surgical maze procedure during catheter ablation of atrial fibrillation, may be created by using laser radiation delivered through flexible diffusing optical fiber tips. Further development of steerable catheters for endocardial atrial ablation and studies correlating thermal damage zones with electrophysiologic indicators of irreversible conduction block are warranted. 相似文献