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51.
Saravanan K Schaeren-Wiemers N Klein D Sandhoff R Schwarz A Yaghootfam A Gieselmann V Franken S 《Neurobiology of disease》2004,16(2):396-406
Metachromatic leukodystrophy (MLD) is a lysosomal lipid storage disease caused by arylsulfatase A deficiency. In MLD patients the sphingolipid sulfatide increasingly accumulates leading to progressive demyelination. We have analysed arylsulfatase A-deficient mice, a MLD mouse model, and we show that accumulation of sulfatide is not restricted to the lysosomal compartment but also occurs in myelin itself. Although, this sulfatide storage did not affect the overall composition of most myelin proteins, it specifically caused a severe reduction of MAL. This demonstrates a regulatory link between sulfatide accumulation and MAL expression and indicates the existence of regulatory mechanisms between lipid and myelin protein synthesis in oligodendrocytes. In addition, in cultured renal epithelial cells, sulfatide accumulation diverts MAL to the late endosomal/lysosomal compartment and thus also affects the intracellular distribution of MAL. The specific reduction and mistargeting of MAL protein as a reaction to sulfatide overload may contribute to the pathogenic mechanisms in metachromatic leukodystrophy. 相似文献
52.
Bone marrow micrometastases and circulating tumor cells: current aspects and future perspectives
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Early tumor cell dissemination at the single-cell level can be revealed in patients with breast cancer by using sensitive
immunocytochemical and molecular assays. Recent clinical studies involving more than 4000 breast cancer patients demonstrated
that the presence of disseminated tumor cells in bone marrow at primary diagnosis is an independent prognostic factor. In
addition, various assays for the detection of circulating tumor cells in the peripheral blood have recently been developed
and some studies also suggest a potential clinical relevance of this measure. These findings provide the basis for the potential
use of disseminated tumor cells in bone marrow or blood as markers for the early assessment of therapeutic response in prospective
clinical trials. 相似文献
53.
Grigorenko EL Klin A Volkmar F 《Journal of child psychology and psychiatry, and allied disciplines》2003,44(8):1079-1091
BACKGROUND: Hyperlexia is the phenomenon of spontaneous and precocious mastery of single-word reading that has been of interest to clinicians and researchers since the beginning of the last century. METHODS: An extensive search of publications on the subject of hyperlexia was undertaken and all available publications were reviewed. RESULTS: The literature can be subdivided into discussions of the following issues: (1) whether hyperlexia is a phenomenon that is characteristic only of specific clinical populations (e.g., children with developmental delays) or whether it can also be observed in the general population; (2) whether hyperlexia is a distinct syndrome comorbid with a number of different disorders or whether it is a part of the spectrum of some other clinical condition(s); (3) whether hyperlexia should be defined through single-word reading superiority with regard to reading comprehension, vocabulary, general intelligence, any combination of the three, or all three characteristics; (4) whether there is a specific neuropsychological profile associated with hyperlexia; (5) whether hyperlexia is characterized by a particular developmental profile; and (6) whether hyperlexia should be viewed as a disability (deficit) or superability (talent). CONCLUSIONS: We interpret the literature as supporting the view that hyperlexia is a superability demonstrated by a very specific group of individuals with developmental disorders (defined through unexpected single-word reading in the context of otherwise suppressed intellectual functioning) rather than as a disability exhibited by a portion of the general population (defined through a discrepancy between levels of single-word reading and comprehension). We simultaneously argue, however, that multifaceted and multi-methodological approaches to studying the phenomenon of hyperlexia, defined within the research framework of understanding single-word reading, are warranted and encouraged. 相似文献
54.
55.
Schneider V Henschel V Tadjalli-Mehr K Mansmann U Haefeli WE 《Clinical pharmacology and therapeutics》2003,74(5):458-467
BACKGROUND: Doses of renally eliminated drugs should be adjusted according to kidney function to prevent adverse drug events and cost. Dose adjustment can be based on serum creatinine level, subsequent creatinine clearance estimation, and dosage calculation with consideration of the renal elimination properties of the respective compound. OBJECTIVE: Our objective was to quantify the impact and relevance of serum creatinine measurement error on dose adjustment in renal failure. METHODS: We analyzed 27914 measurements from external quality assessment surveys of 1878 German laboratories that used a kinetic alkaline picrate (69% of results) or an enzymatic method (25%) for creatinine determination. Linear models were fit for both methods combined and separately. On the basis of 95% confidence intervals (CIs) for creatinine values, 95% CIs for drug dosing were calculated. RESULTS: The 95% CI for a measured serum creatinine value was 0.80. Measured value < Reference method value < 1.28. Measured value for the kinetic alkaline picrate method and 0.87. Measured value < Reference method value < 1.21. Measured value for the enzymatic method. Applied to a data set of 6.5 million simulated patients with all possible combinations of characteristics relevant for drug dosing, the dosing error caused by serum creatinine measurement error did not exceed 25% in patients with creatinine clearance estimates lower than 50 mL/min according to the Cockcroft-Gault equation. For drugs completely eliminated by the kidneys in active form, the dosing error was up to 6-fold smaller than that which would occur if doses were not adjusted. CONCLUSION: The serum creatinine measurement error of current laboratory methods is small and is comparable to other errors influencing dose adjustment. 相似文献
56.
Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor 总被引:21,自引:0,他引:21
57.
Kristof RA Aliashkevich AF Hans V Haun D Meyer B Thees C Schramm J 《Neurosurgery》2003,53(4):880-5; discussion 885-6
OBJECTIVE: To study the regional oxygen saturation (rSO(2)) of pituitary adenomas, in comparison with that of the pituitary gland. METHODS: Microspectrophotometric (MSP) measurements of rSO(2) in adenomas and pituitary tissue were performed for a series of patients undergoing first-time transsphenoidal pituitary adenoma surgery, in a standardized anesthesia setting. The areas of measured tissue were sampled for histopathological and immunohistochemical (CD34 and CD45) assessments. The results of MSP measurements were compared with the results of the histopathological and immunohistochemical assessments. RESULTS: Thirty-six MSP measurements and tissue samples were obtained among 22 patients with pituitary macroadenomas, including 14 from adenoma tissue, 17 from the anterior pituitary lobe, and 5 from the posterior pituitary lobe. The rSO(2) of adenoma tissue (mean +/- standard deviation, 43.3 +/- 23.2%) was statistically significantly (P = 0.001) lower than the values for the anterior pituitary lobe (mean +/- standard deviation, 71.8 +/- 18.3%) and posterior pituitary lobe (mean +/- standard deviation, 74.9 +/- 4.8%). The difference between the rSO(2) values for the anterior pituitary lobe and posterior pituitary lobe was not significant. There were no statistically significant differences in microvessel density (as assessed with CD34 staining) or lymphocyte density (as assessed with CD45 staining) among the three tissue types. CONCLUSION: As assessed with MSP measurements, the rSO(2) of adenoma tissue was significantly lower than that of the pituitary gland, indicating differences in their blood supply and/or metabolism in pituitary macroadenomas. Further studies are needed to determine whether MSP measurements can reliably facilitate intraoperative delineation of adenoma and pituitary tissue, in the effort to achieve complete tumor removal with minimal injury to pituitary tissue. 相似文献
58.
Secundum ASD closure using a right lateral minithoracotomy: five-year experience in 122 patients 总被引:5,自引:0,他引:5
Doll N Walther T Falk V Binner C Bucerius J Borger MA Gummert JF Mohr FW Kostelka M 《The Annals of thoracic surgery》2003,75(5):1527-30; discussion 1530-1
BACKGROUND: Surgical closure of secundum atrial septal defect (ASD) is a standard procedure associated with very low mortality and morbidity. We evaluated outcomes in the era of catheter-based interventional closure and minimally invasive techniques. METHODS: From May 1996, February 2002, 177 patients with a body weight of more than 30 kg underwent surgical ASD closure. A right lateral minithoracotomy (LMT) was used in 122 patients and a conventional approach, in 55. Diagnoses included secundum ASD in 106 patients in the LMT group and 40 in the conventional group, sinus venosus ASD in 13 patients in each group, and status post interventional closure in 3 and 2 patients, respectively. Mean age was 37 +/- 17 years in the LMT group and 43 +/- 20 years, in the conventional group and mean body weight was 66 +/- 17 kg and 70 +/- 16 kg, respectively. In the LMT group, femoral cannulation was performed for cardiopulmonary bypass. RESULTS: Direct ASD closure was carried out in 67.2% of patients in the LMT group and 58.2% of those in the conventional group. The remaining patients had pericardial patch closure. There was one death: A patient in the conventional group who required explantation of an Amplatzer device because of infection died postoperatively. Average stay in the intensive care unit was 1.2 +/- 0.5 days. Two patients required reoperation for residual ASD after direct closure; 1 sustained a temporary neurological deficit that resolved completely. On postoperative echocardiography, a minimal residual shunt was seen in only 3 patients. All patients were in good clinical condition with improved functional status at discharge from the hospital. CONCLUSIONS: Secundum ASD closure by LMT has become as standard and safe an operation as the conventional technique and achieves good perioperative results and satisfactory long-term outcomes. Thus LMT is an attractive option for patients who are not suitable for closure using catheter-based devices. 相似文献
59.
Stephan Jacobs MD David Holzhey MD Bob B Kiaii MD Joerg F Onnasch MD Thomas Walther MD PhD Friedrich W Mohr MD PhD Volkmar Falk MD PhD 《The Annals of thoracic surgery》2003,76(6):2029-2035
Background
Surgical performance is limited by human factors. Beating-heart surgery requires full dexterity and motion tracking. Currently techniques for total endoscopic beating-heart bypass grafting using telemanipulation systems are being developed. The aim of this study was to assess the limitations for manual and telemanipulator-assisted motion tracking using the da Vinci telemanipulator system.Methods
To simulate beating-heart conditions an endoscopic trainer was developed. Twenty subjects were asked to touch targets manually and with telemanipulator assistance with different patterns of increasing index of difficulty (resting model, unstabilized, and stabilized model with a frequency of 35, 60, and 90 beats per minute). In addition one task was performed using different scaling ratios on a resting model. The times between hits as well as errors were electronically recorded.Results
There was no significant impact of various frequencies and amplitudes for manual tracking. The average values for the delay (km[ms]) and information-processing (cm [ms/bit]) constants for the manual tasks were 201 ms and 86 ms/bit respectively. Both the delay constant (kt = 630 ms; p < 0.0005) and the information-processing constant (ct = 250 ms/bit; p < 0.0005) were increased for the telemanipulator-assisted tasks at rest. When working on moving targets telemanipulator-assisted tracking required significantly more time and led to more errors. At a frequency of 90 beats per minute telemanipulator-assisted tracking became more difficult.Conclusions
Endoscopic beating-heart bypass grafting requires optimal stabilization to avoid inaccuracies due to incomplete motion tracking. At higher frequencies telemanipulator-assisted tracking became more difficult, demonstrating the technical limits of current telemanipulator technology. 相似文献60.
Galactography should only be performed if there is spontaneous bloody or serous discharge from a single lactiferous duct of
one breast. If this is observed, only pathologic processes instead of normal breast tissue are removed upon surgery and there
is a close correlation between radiologic results and pathologic findings. Galactography localizes intraductal pathologic
processes precisely and thus contributes to minimal volume surgery. 相似文献