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61.
Susanne Rinné Vijay Renigunta Günter Schlichthörl Marylou Zuzarte Stefan Bittner Sven G. Meuth Niels Decher Jürgen Daut Regina Preisig-Müller 《Pflügers Archiv : European journal of physiology》2014,466(8):1559-1570
We have identified a novel splice variant of the human and rat two-pore domain potassium (K2P) channel TREK-1. The splice variant TREK-1e results from skipping of exon 5, which causes a frame shift in exon 6. The frame shift produces a novel C-terminal amino acid sequence and a premature termination of translation, which leads to a loss of transmembrane domains M3 and M4 and of the second pore domain. RT-PCR experiments revealed a preferential expression of TREK-1e in kidney, adrenal gland, and amygdala. TREK-1e was nonfunctional when expressed in Xenopus oocytes. However, both the surface expression and the current density of full-length TREK-1 were reduced by co-expression of TREK-1e. Live cell imaging in COS-7 cells transfected with GFP-tagged TREK-1e showed that this splice variant was retained in the endoplasmic reticulum (ER). Attachment of the C-terminus of TREK-1e to two different reporter proteins (Kir2.1 and CD8) led to a strong reduction in the surface expression of these fusion proteins. Progressive truncation of the C-terminus of TREK-1e in these reporter constructs revealed a critical region (amino acids 198 to 205) responsible for the intracellular retention. Mutagenesis experiments indicated that amino acids I204 and W205 are key residues mediating the ER retention of TREK-1e. Our results suggest that the TREK-1e splice variant may interfere with the vesicular traffic of full-length TREK-1 channels from the ER to the plasma membrane. Thus, TREK-1e might modulate the copy number of functional TREK-1 channels at the cell surface, providing a novel mechanism for fine tuning of TREK-1 currents. 相似文献
62.
Lusine Nazaryan Eunice G Stefanou Claus Hansen Nadezda Kosyakova Mads Bak Freddie H Sharkey Theodora Mantziou Anastasios D Papanastasiou Voula Velissariou Thomas Liehr Maria Syrrou Niels Tommerup 《European journal of human genetics : EJHG》2014,22(3):338-343
Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes. 相似文献
63.
Shengting Li Soren Besenbacher Yingrui Li Karsten Kristiansen Niels Grarup Anders Albrechtsen Thomas Spars? Thorfinn Korneliussen Torben Hansen Jun Wang Rasmus Nielsen Oluf Pedersen Lars Bolund Mikkel H Schierup 《European journal of human genetics : EJHG》2014,22(8):1040-1045
In this paper, we mine full mtDNA sequences from an exome capture data set of 2000 Danes, showing that it is possible to get high-quality full-genome sequences of the mitochondrion from this resource. The sample includes 1000 individuals with type 2 diabetes and 1000 controls. We characterise the variation found in the mtDNA sequence in Danes and relate the variation to diabetes risk as well as to several blood phenotypes of the controls but find no significant associations. We report 2025 polymorphisms, of which 393 have not been reported previously. These 393 mutations are both very rare and estimated to be caused by very recent mutations but individuals with type 2 diabetes do not possess more of these variants. Population genetics analysis using Bayesian skyline plot shows a recent history of rapid population growth in the Danish population in accordance with the fact that >40% of variable sites are observed as singletons. 相似文献
64.
Lena Hanberger Niels Birkebaek Ragnar Bjarnason Ann Kristin Drivvoll Anders Johansen Torild Skrivarhaug Arni V. Thorsson Ulf Samuelsson 《Journal of diabetes science and technology》2014,8(4):738-744
Background:In 2008 a Nordic collaboration was established between the quality registries in Denmark, Iceland, Norway, and Sweden to improve quality of care for children with diabetes. This study aimed to describe those registries and confirm that the registry variables are comparable. Selected variables were used to demonstrate outcome measurements.Methods:The organization of the registries and methodology are described. Cross-sectional data for patients between birth and 14.9 years with type 1 diabetes mellitus in 2009 (n = 6523) from 89 centers were analyzed. Variables were age, gender, and diabetic ketoacidosis at onset, together with age, gender, HbA1c, insulin regimen, and severe hypoglycemia at follow-up in 2009.Results:All 4 registries use a standardized registration at the onset of diabetes and at follow-up, conducted at the local pediatric diabetes centers. Methods for measuring HbA1c varied as did methods of registration for factors such as hypoglycemia. No differences were found between the outcomes of the clinical variables at onset. Significant variations were found at follow-up for mean HbA1c, the proportion of children with HbA1c < 57 mmol/mol (NGSP/DCCT 7.4%), (range 15-31%), the proportion with insulin pumps (range 34-55%), and the numbers with severe hypoglycemia (range 5.6-8.3/100 patient years).Conclusions:In this large unselected population from 4 Nordic countries, a high proportion did not reach their treatment target, indicating a need to improve the quality of pediatric diabetes care. International collaboration is needed to develop and harmonize quality indicators and offers possibilities to study large geographic populations, identify problems, and share knowledge. 相似文献
65.
Dirk Halama Ruth Dreilich Bernd Lethaus Alexander Bartella Niels Christian Pausch 《Journal of cranio-maxillo-facial surgery》2019,47(12):1980-1985
IntroductionRadial forearm free flaps (RFFF) are often used to replace tissue removed in head and neck surgery. In recent years, many attempts have been made to reduce donor-site morbidity and to prevent common complications such as infection, skin-graft necrosis, tendon exposure and subsequent impairment of hand function. One promising option is the use of vacuum-assisted-closure wound therapy (VAC). The objective of this study was to evaluate the effectiveness of VAC compared with a conventional bolster dressing (CBD).Material and methodsA randomized controlled trial was enrolled. Our study was prospective in design and included patients with a skin-grafted forearm defect after harvesting of RFFF. Patients who met the inclusion criteria were randomly assigned into two study arms. The predictor variable was the type of wound therapy (VAC therapy compared with CBD) and the outcome variables were (1) the size of the wound area, (2) wrist movement and (3) grip strength. Outcome variables were assessed 12 days, three weeks and eight weeks after surgery.ResultsFifty patients (33 males, mean age 61.7 years [SD 15.5]; 17 females, mean age 54.7 years [SD 10.5]) were included consecutively in the study. Patients in the VAC group experienced a faster postsurgical reduction of wound area and had better wrist movement; nonetheless, the differences between the VAC group and CBD group did not reach statistical significance. In contrast, the recovery of postsurgical grip strength was significantly faster in the VAC group.ConclusionsOur study failed to prove that VAC therapy is significantly superior to CBD for all the variable studied. Because VAC therapy has some positive effects, however, we recommend further development of this negative-pressure wound treatment, rather than the termination of its use. 相似文献
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70.
Gierloff M Seeck NG Springer I Becker S Kandzia C Wiltfang J 《The Journal of craniofacial surgery》2012,23(1):161-164
Many different materials are proposed for reconstruction of traumatic orbital floor defects. Donor-site morbidity of autologous transplants and infections or extrusions of nonresorbable implants lead to a widespread use of resorbable, alloplastic materials such as polydioxanone (PDS). The goal of this study was to evaluate the prevalence of orbital floor fracture-related problems after surgical treatment using PDS. Ophthalmologic and clinical examinations were performed at 194 patients before orbital floor reconstruction, 14 days and 6 months after surgery (approximate defect sizes: <1 cm2, n=50; 1-2 cm2, n=97; >2 cm2, n=47). Clinical findings including the ocular motility, the sensibility of the infraorbital nerve, and the position of the globe were evaluated. For statistical analysis of categorical data, confidence intervals of percentages were determined. Linear relationships between 2 variables were assessed with Pearson correlation analysis. A reduced ocular motility was diagnosed in 60 patients (31%) before surgery; in 14 patients (7%), 2 weeks; and in 10 patients (5%), 6 months after surgery. Infraorbital hypesthesia was found in 120 patients (62%) before surgery; in 47 patients (24%), 2 weeks; and in 35 patients (18%), 6 months after surgery. An enophthalmos was present in 10 patients (5%) before surgery, and in 4 patients (2%), 6 months after surgery. Our data suggest that PDS is a suitable implant for orbital floor reconstruction with acceptable low rates of infraorbital hypesthesia, bulbus motility disturbances, and enophthalmos. Polydioxanone can also be used for orbital floor defects exceeding 2 cm2. 相似文献