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Background Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.Methods The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated.Results Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours.Conclusions FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases.ClinicalTrials.gov identifier NCT00433927.Subject terms: Oncology, Biomarkers  相似文献   
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In minimally invasive surgery methods such as laparoscopic surgery, surgical instruments are introduced through small incisions to minimize patient trauma and recovery times. To reduce the number of incisions, new techniques such as natural orifice transluminal endoscopic surgery (NOTES) have been proposed. Compared to laparoscopic surgery, the NOTES approach, which requires new technology and improved instruments, presents some unique challenges. Robotic NOTES (R-NOTES) could be an enabling technology for these procedures. In this paper, we first review relevant work in R-NOTES. We then present our work and the system architecture for an R-NOTES prototype system incorporating wireless command and control. The system was tested twice in swine animal studies.  相似文献   
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Graefe's Archive for Clinical and Experimental Ophthalmology - The published online version contains mistake as the author's first name and last name have been interchanged as "Hild...  相似文献   
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Die Anaesthesiologie - Die COVID-19-Pandemie hat das deutsche Gesundheitssystem vor enorme Herausforderungen gestellt und den Bedarf an Strategien zu Rekrutierung, Schulung und Einsatzplanung von...  相似文献   
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Extracellular vesicles (EV) are secreted signaling entities that enhance various pathological processes when released in response to cellular stresses. Respiratory exposures such as cigarette smoke and air pollution exert cellular stresses and are associated with an increased risk of several chronic diseases. The aim of this review was to examine the evidence that modifications in EV contribute to respiratory exposure-associated diseases. Publications were searched using PubMed and Google Scholar with the search terms (cigarette smoke OR tobacco smoke OR air pollution OR particulate matter) AND (extracellular vesicles OR exosomes OR microvesicles OR microparticles OR ectosomes). All original research articles were included and reviewed. Fifty articles were identified, most of which investigated the effect of respiratory exposures on EV release in vitro (25) and/or on circulating EV in human plasma (24). The majority of studies based their main observations on the relatively insensitive scatter-based flow cytometry of EV (29). EV induced by respiratory exposures were found to modulate inflammation (19), thrombosis (13), endothelial dysfunction (11), tissue remodeling (6), and angiogenesis (3). By influencing these processes, EV may play a key role in the development of cardiovascular diseases and chronic obstructive pulmonary disease and possibly lung cancer and allergic asthma. The current findings warrant additional research with improved methodologies to evaluate the contribution of respiratory exposure-induced EV to disease etiology, as well as their potential as biomarkers of exposure or risk and as novel targets for preventive or therapeutic strategies.  相似文献   
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The objective of this study was to investigate whether it is possible to use a lateral (profile) photograph to determine the underlying skeletal Class and which reference points of the angle of convexity are most suitable for this purpose. Profile photographs and lateral cephalographs included in the baseline data for 180 orthodontic patients were retrospectively evaluated. The subjects were assigned to skeletal Classes based on Wits values obtained by radiolographic analysis. The Class I subjects were 58 patients (22 males, 36 females) with an average age of 13.63 +/- 2.1 years, the Class II subjects 60 patients (37 males, 23 females) with an average age of 13.60 +/- 2.6 years, and the Class III subjects 62 patients (28 males, 34 females) with an average age of 11.65 +/- 3.3 years. The angles measured were A'OrB' (=POrA'-POrA'), A'N'B', and the angle of convexity with its variants (N'SnPog', N'A'Pog', TrSnPog', TrA'Pog', Gl'SnPog', and Gl'A'Pog'). These angles were statistically evaluated using a two-sided t-test and linear discriminant analysis. Class II and Class III subjects exhibited highly significant differences (P < 0.001) for all angles. Class I and Class III exhibited highly significant differences (P < 0.001) for almost all angles, and significant differences for A'N'B' (P < 0.05). Class I and Class II differed significantly (P < 0.05) only for some angles (N'SnPog', TrA'Pog', Gl'SnPog', and Gl'A'Pog'). The error within the linear discriminant analysis was smallest for N'SnPog', GlA'Pog', and TrA'Pog' angles. However, the method error according to Dahlberg yielded rather high values for all angles (1.07-1.17 degrees). Discrimination between skeletal Class I and Class III was easier than that between Class I and Class II. One of the reasons may be that the subclasses division I and division II were not distinguished within the Class II subjects.  相似文献   
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This review article addresses the question as to what methods can be used to investigate cranial structure and growth development in children 4 to 6 years old, and what the relevant reference values are for this age group. We screened the literature for epidemiological, longitudinal and cross-sectional studies investigating healthy children 4 to 6 years old without abnormalities and orthodontic therapy. Radiographic cephalometry is a practical, valid tool for analyzing craniofacial structure and growth processes. But it has several disadvantages, including the use of ionizing radiation, measuring points that are difficult to locate, no means of radiographic enlargement without distorting reference values, and the data's two-dimensionality. Anthropometry is another procedure for creating reference values for the craniofacial structure in children. Its advantages over radiographic cephalometry include three-dimensional results and no radiation exposure. Moreover, it yields precise and valid results for a wide variety of potential applications.In addition to these procedures, there are other techniques with which cranial structure and growth development in children 4 to 6 years old can be investigated. Those reported in the literature in this connection include standardized photographs, the creation of computerized and magnetic resonance images, and investigations performed on dry skulls. In short, there is great demand nowadays for investigations aimed at developing reference values for Caucasian children 4 to 6 years old. Radiographic cephalometry and anthropometry are two very common methods. Anthropometry is expected to become increasingly important because it involves no exposure to radiation.  相似文献   
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