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排序方式: 共有2258条查询结果,搜索用时 62 毫秒
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Ladan Kobari Frank Yates Noufissa Oudrhiri Alain Francina Laurent Kiger Christelle Mazurier Shaghayegh Rouzbeh Wassim El-Nemer Nicolas Hebert Marie-Catherine Giarratana Sabine Fran?ois Alain Chapel Hélène Lapillonne Dominique Luton Annelise Bennaceur-Griscelli Luc Douay 《Haematologica》2012,97(12):1795-1803
Background
Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors.Design and Methods
We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation.Results
We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice.Conclusions
These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment.Key words: human induced pluripotent stem cells, terminal maturation, erythropoietic differentiation 相似文献65.
Lucie Plomhause Kathy Dujardin Alain Duhamel Marie Delliaux Philippe Derambure Luc Defebvre Christelle Monaca Charley 《Sleep medicine》2013,14(10):1035-1037
Objective
Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for dementia in Parkinson disease (PD) patients. The objectives of our study were to prospectively evaluate the frequency of RBD in a sample of treatment-naïve, newly diagnosed PD patients and compare sleep characteristics and cognition in RBD and non-RBD groups.Methods
Fifty-seven newly diagnosed PD patients were consecutively recruited in a university medical center. All patients underwent two overnight polysomnography (PSG) sessions and were diagnosed with RBD according to the International Classification of Sleep Disorders, Second Revision criteria. Daytime sleepiness was measured in a multiple sleep latency test (MSLT). Cognition was assessed in a standard neuropsychologic examination.Results
Seventeen PD patients (30%) met the criteria for RBD. The RBD patients and non-RBD patients did not significantly differ in mean age, gender ratio, disease duration, motor symptom subtype and severity, total sleep time, percentage of REM sleep, apnea–hypopnea index, mean oxygen saturation, and importantly cognitive performance. However, non-RBD patients had a significantly shorter mean daytime sleep latency than RBD patients (15 vs 18 min, respectively; P = .014).Conclusion
A high frequency of RBD was found in our sample of 57 newly diagnosed PD patients. At this stage in the disease, RBD was not found to be associated with other sleep disorders or cognitive decline. Follow-up is needed to assess the risk for developing dementia in early-stage PD patients with RBD. 相似文献66.
Melanie Boerries Florian Grahammer Sven Eiselein Moritz Buck Charlotte Meyer Markus Goedel Wibke Bechtel Stefan Zschiedrich Dietmar Pfeifer Denis Laloë Christelle Arrondel Sara Gonçalves Marcus Krüger Scott J. Harvey Hauke Busch Joern Dengjel Tobias B. Huber 《Kidney international》2013,83(6):1052-1064
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A randomized, double-blind, placebo-controlled, cross-over, dose-escalating, single-center study was conducted to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of multiple once-daily (qd) subcutaneous (sc) doses of pasireotide in healthy male subjects. Subjects received pasireotide 50, 200, or 600?μg?sc?qd for 14?days and placebo in separate sequences. Thirty-three subjects were randomized. The most frequently reported drug-related adverse events were injection-site reactions (n?=?18), diarrhea (n?=?14) and nausea (n?=?10), which were mostly mild or moderate in intensity. Pasireotide 600?μg?sc was associated with pre- and post-prandial elevations in glucose levels relative to placebo; however, this effect was less pronounced on day 14 compared with day 1. PK steady state appeared to be achieved after 3?days of dosing and PK exposures had a moderate accumulation of 20-40?% across doses. Pasireotide demonstrated fast absorption (T (max,ss): 0.25-0.5?h), low clearance (CL/F (ss): 8.10-9.03?L/h), long effective half-life (T (?,eff): ~12?h, on average between 9.7 and 13.1?h for 50, 200, and 600?μg?sc?qd), and large volume of distribution (V (z)/F (ss): 251-1,091?L) at steady state. Dose proportionality was confirmed for C (max,ss); other PK parameters (C (max), AUC(0-24?h) and AUC(tau)) were approximately dose proportional. Growth hormone inhibition was observed with pasireotide 200 and 600?μg?sc?qd. Gallbladder volume increased post-prandially with pasireotide 200 and 600?μg?sc?qd, which appeared to correlate with reduced levels of cholecystokinin at these doses. Pasireotide was generally well tolerated up to the tested dose of 600?μg?qd, with a linear and time-independent PK profile after sc qd dosing in healthy subjects. 相似文献
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Stéphanie Rignault-Clerc Christelle Bielmann Frederik Delodder Wassim Raffoul Bernard Waeber Lucas Liaudet Mette M. Berger François Feihl Nathalie Rosenblatt-Velin 《Burns : journal of the International Society for Burn Injuries》2013