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41.
A controversial proposal to collapse sexual disorders of desire and arousal is forthcoming in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) (DSM-5). Yet, no study has attempted to empirically distinguish these disorders by using explicit criteria to recruit and compare distinct groups of low desire and arousal sufferers. The goal of the current study was to test the feasibility of finding medically healthy men and women meeting clearly operationalized DSM-IV-TR criteria for disorders of desire and/or arousal and compare them to matched controls. To assess operational criteria, participants completed a comprehensive telephone screening interview assessing DSM-IV-TR and DSM-5 criteria, as well as standardized self-report measures of sexual functioning. The use of operationalized DSM-IV-TR criteria to recruit participants led to the exclusion of over 75 % of those reporting sexual difficulties, with the primary reason for exclusion being failure to meet at least one central diagnostic criterion. The application of the DSM-5 criteria was even more restrictive and led to the exclusion of all but four men and one woman using the original four-symptom criteria, and four men and five women using the revised three-symptom criteria. Cluster analyses supported the distinction between desire and genital arousal difficulties, and suggest that different groups with distinct clusters of symptoms may exist, two of which are consistent with the DSM-5 criteria. Overall, results highlight the need for revisions to the diagnostic criteria, which, as they stand, do not capture the full range of many people’s sexual difficulties. 相似文献
42.
Although melanoma has traditionally been regarded as a uniformly fatal malignancy, personalized treatment of this cancer relies on the recognition of its genetic heterogeneity and our ability to pharmacologically target these specific and recurrent changes. Recent advances in the treatment of melanoma have come from the understanding that melanoma is a large family of molecularly distinct diseases. Advances in melanoma genetics and new molecular technology, such as whole-exome and whole-genome sequencing, have lead to unprecedented progress in understanding the key oncogenes and signaling pathways involved in the pathogenesis and progression of melanoma. In addition, we have gained an appreciation for the complexity of such a system with numerous points of cross talk, which has partially impeded our current therapeutic strategies in patients with advanced melanoma. In this review, we focus on the novel discoveries in melanoma genetics and the potential for therapeutic options. 相似文献
43.
Sabina Martí Gamboa Jara Pascual Mancho María Rodrigo Rodríguez Julia Ruiz Sada Sergio Castán Mateo 《The journal of maternal-fetal & neonatal medicine》2017,30(19):2367-2371
Objective: To determine which parameter of the umbilical arterial cord gas analysis, pH, base deficit (BD) or lactate has a bigger predictive ability for neonatal morbidity at term.Method: We conducted a four-year retrospective cohort study including all non-anomalous, singleton, vertex, term births with neonatal acidemia (umbilical arterial cord gas pH?≤?7.1). The primary outcomes were a composite neurological morbidity and a composite systemic morbidity. The predictive ability of lactate, BD and pH was compared using receiver operator characteristic (ROC) curves. Optimal cutoff values of lactate, BD and pH were estimated based on their maximal Youden Index.Results: We identified 466 acidemic neonates who had paired and validated cord blood gas data. The ROC curve analysis revealed that pH, BD and lactate had a similar predictive ability for neurological (AUC: 0.81; 0.78; 0.83, respectively) and systemic neonatal morbidity (AUC: 0.77; 0.82; 0.82, respectively). The combination of pH?≤?7.0 and lactate?≥?7.0?mmol/L presented similar validity to that of pH?≤?7.0 and BD?≥?12?mmol/L, but both were comparable to pH alone.Conclusions: pH, BD and lactate have similar predictive ability for adverse neonatal outcomes among acidemic neonates. Umbilical arterial lactate could replace BD as a measure of the metabolic component in acidemic neonates. However, neither BD nor lactate demonstrated in this study to improve the predictive ability of pH alone for short-term neonatal outcomes. 相似文献
44.
Sabina Gallati Simone Hess Dorothea Galié-Wunder Elisabeth Berger-Menz Dominik Böhlen 《Reproductive biomedicine online》2009,18(5):685-694
The objective of this study was to investigate the contribution of cystic fibrosis transmembrane conductance regulator (CFTR) to human infertility and to define screening and counselling procedures for couples asking for assisted reproduction treatment. Extended CFTR mutation screening was performed in 310 infertile men (25 with congenital absence of the vas deferens (CAVD), 116 with non-CAVD azoospermia, 169 with severe oligospermia), 70 female partners and 96 healthy controls. CFTR mutations were detected in the majority (68%) of CAVD patients and in significant proportions in azoospermic (31%) and oligospermic (22%) men. Carrier frequency among partners of infertile men was 16/70, exceeding that of controls (6/96) significantly (P = 0.0005). Thus, in 23% of infertile couples both partners were carriers, increasing the risk for their offspring to inherit two mutations to 25% or 50%. This study emphasizes the necessity to offer extended CFTR mutation screening and counselling not only to patients with CAVD but also to azoospermic and oligozoospermic men and their partners before undergoing assisted reproduction techniques. The identification of rare and/or mild mutations will not be a reason to abstain from parenthood, but will allow adequate treatment in children at risk for atypical or mild cystic fibrosis as soon as they develop any symptoms. 相似文献
45.
Ruan B Palioura S Sabina J Marvin-Guy L Kochhar S Larossa RA Söll D 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(43):16502-16507
A high level of accuracy during protein synthesis is considered essential for life. Aminoacyl-tRNA synthetases (aaRSs) translate the genetic code by ensuring the correct pairing of amino acids with their cognate tRNAs. Because some aaRSs also produce misacylated aminoacyl-tRNA (aa-tRNA) in vivo, we addressed the question of protein quality within the context of missense suppression by Cys-tRNA(Pro), Ser-tRNA(Thr), Glu-tRNA(Gln), and Asp-tRNA(Asn). Suppression of an active-site missense mutation leads to a mixture of inactive mutant protein (from translation with correctly acylated aa-tRNA) and active enzyme indistinguishable from the wild-type protein (from translation with misacylated aa-tRNA). Here, we provide genetic and biochemical evidence that under selective pressure, Escherichia coli not only tolerates the presence of misacylated aa-tRNA, but can even require it for growth. Furthermore, by using mass spectrometry of a reporter protein not subject to selection, we show that E. coli can survive the ambiguous genetic code imposed by misacylated aa-tRNA tolerating up to 10% of mismade protein. The editing function of aaRSs to hydrolyze misacylated aa-tRNA is not essential for survival, and the EF-Tu barrier against misacylated aa-tRNA is not absolute. Rather, E. coli copes with mistranslation by triggering the heat shock response that stimulates nonoptimized polypeptides to achieve a native conformation or to be degraded. In this way, E. coli ensures the presence of sufficient functional protein albeit at a considerable energetic cost. 相似文献
46.
Estimation of the false-negative rate in newborn screening for congenital adrenal hyperplasia 总被引:2,自引:0,他引:2
Votava F Török D Kovács J Möslinger D Baumgartner-Parzer SM Sólyom J Pribilincová Z Battelino T Lebl J Frisch H Waldhauser F;Middle European Society for Paediatric Endocrinology -- Congenital Adrenal Hyperplasia 《European journal of endocrinology / European Federation of Endocrine Societies》2005,152(6):869-874
OBJECTIVE: Newborn screening based on measurement of 17alpha-hydroxyprogesterone (17-OHP) in a dried blood spot on filter paper is an effective tool for early diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Its most important rationale is prevention of a life-threatening salt-wasting (SW) crisis; in moderate forms of CAH, early diagnosis and treatment may prevent permanent negative effects of androgen overproduction. Our target was to analyse if all CAH patients who had been identified clinically before puberty would have been detected by the newborn screening. METHODS: Newborn screening cards of 110 CAH patients born between 1988 and 2000 in five Middle-European countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from 920 random, healthy newborn controls were analysed. CAH screening had not yet been introduced during this time. The diagnosis was based on clinical and laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP measurements in dried blood spots were carried out using a time-resolved fluoroimmunoassay kit. RESULTS: In the newborn screening blood spots, the median of 17-OHP levels was 561 nmol/l (range 91-1404 nmol/l) in subjects with the SW form and 40 nmol/l (4-247 nmol/l) in the moderate form. All 77 SW patients would have been detected by newborn screening using the recommended cut-off limits (30 nmol/l). However, 10 of 33 patients with moderate CAH would have been missed. 17-OHP levels of all controls were below the cut-off. CONCLUSION: Newborn screening is efficient for diagnosing the SW form of CAH, but is inappropriate for identifying all patients with a moderate form of CAH. It appears that the false-negative rate is at least one-third in children with the moderate form of CAH. 相似文献
47.
Ajay J Kirtane Jonathan J Vafai Sabina A Murphy Julian M Aroesty Marc S Sabatine Christopher P Cannon C Michael Gibson 《European heart journal》2006,27(17):2040-2045
AIMS: The presence of residual thrombus following fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI) may predispose to greater embolization and microvascular dysfunction. METHODS AND RESULTS: We hypothesized that even in the presence of a patent epicardial artery, residual thrombus would be associated with worsened TIMI myocardial perfusion grades (TMPG), independent of epicardial flow. Data were analysed from the angiograms of 2684 patients enrolled in the CLARITY-TIMI 28 trial, with angiographically patent arteries (TIMI 2/3 flow) at a median of 88 h following fibrinolytic therapy. Thrombus in a patent epicardial artery was observed more frequently among patients with shorter times from randomization to angiography, among patients with non-left anterior descending infarctions, and among patients treated with placebo (vs. clopidogrel). Thrombus was associated with more frequent TIMI 2 flow (35.1 vs. 22.1%, P < 0.001), higher corrected TIMI frame counts (CTFC) (42 vs. 33 frames, P < 0.001), and a lower incidence of normal TMPG 3 (48.7 vs. 63.9%, P < 0.001), irrespective of treatment with clopidogrel or placebo. In multivariable analyses, thrombus remained associated with higher CTFC (P < 0.001) and worse TMPG (OR 1.6 for TMPG 0/1/2, P < 0.001) after adjustment for baseline covariates as well as known correlates of TMPG. The association between thrombus and impaired TMPG remained even after further adjustment for CTFC or TIMI flow grade. CONCLUSION: Residual angiographic thrombus following fibrinolytic therapy in STEMI patients is associated with impaired myocardial perfusion, independent of epicardial flow. This finding emphasizes the roles of platelet aggregation and distal embolization in the pathogenesis of microvascular dysfunction in STEMI. 相似文献
48.
Gibson CM Karha J Murphy SA James D Morrow DA Cannon CP Giugliano RP Antman EM Braunwald E;TIMI Study Group 《Journal of the American College of Cardiology》2003,42(1):7-16
OBJECTIVES: We hypothesized that early recurrent myocardial infarction (MI) following fibrinolytic administration would be assessed with higher mortality at both 30 days and 2 years. BACKGROUND: Although early recurrent MI after fibrinolytic therapy has been associated with increased early mortality in the acute MI setting, its relation to long-term mortality has not been fully explored. METHODS: Mortality data were ascertained in 20,101 patients enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 4, 9, and 10B and Intravenous NPA for the Treatment of Infarcting Myocardium Early (InTIME-II) acute MI trials. RESULTS: The frequency of symptomatic recurrent MI during the index hospitalization was 4.2% (836/20,101). Recurrent MI during the index hospital period was associated with increased 30-day mortality (16.4% [137/836] vs. 6.2% [1,188/19,260], p < 0.001). Likewise, recurrent MI was associated with a sustained increase in mortality up to two years, even after adjustments were made for covariates known to be associated with mortality and recurrent MI (hazard ratio 2.11, p < 0.001). However, this higher mortality at 2 years was due to an early divergence in mortality by 30 days and was not due to a significant increase in late mortality between 30 days and 2 years (4.38% [31/707] vs. 3.76% [685/18,206], p = NS). Percutaneous coronary intervention during the index hospitalization was associated with a lower rate of in-hospital recurrent MI (1.6% vs. 4.5%, p < 0.001) and lower two-year mortality (5.6% vs. 11.6%, p < 0.001). Performance of coronary artery bypass graft surgery was also associated with a lower recurrent rate of MI (0.7% vs. 4.3%, p < 0.001) and lower two-year mortality rate (7.95% vs. 10.6%, p = 0.0008). CONCLUSIONS: Early recurrent MI is associated with increased mortality up to two years. However, most deaths occur early, and the risk of additional deaths between the index hospital period and two years was not significantly increased among patients with recurrent MI. Percutaneous coronary intervention during the index hospitalization was associated with a lower risk of recurrent MI and a lower risk of two-year mortality. 相似文献
49.
Giugliano RP Sabatine MS Gibson CM Roe MT Harrington RA Murphy SA Morrow DA Antman EM Braunwald E 《The American journal of cardiology》2004,93(11):1362-7, A5-6
The restoration of epicardial and myocardial flow remains the primary goal of reperfusion therapy in patients with ST-segment elevation myocardial infarction, but the optimal method to assess this goal has not been defined. Thrombolysis In Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST-segment resolution (STRes) were combined to formulate a new measure of successful reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3 recent phase II clinical trials of ST-segment elevation myocardial infarction. Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before any intervention) after the initiation of reperfusion therapy. The complete restoration of perfusion, or the "trifecta," defined as the presence of TFG 3, MPG 3, and complete (> or =70%) STRes, occurred in 117 patients (18%). The achievement of this trifecta was associated with low rates of 30-day mortality (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs 7.1%, p = 0.01), and the combination of death or CHF (0.9% vs 10.7%, p = 0.001). When the results were stratified with respect to subsequent percutaneous coronary intervention (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI. The achievement of TFG 3, MPG 3, and complete STRes at 60 minutes after fibrinolytic therapy and before PCI occurred in only 18% of patients but was associated with very low rates of death and CHF at 30 days. This new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography. 相似文献
50.