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991.
Li J Humphreys K Darabi H Rosin G Hannelius U Heikkinen T Aittomäki K Blomqvist C Pharoah PD Dunning AM Ahmed S Hooning MJ Hollestelle A Oldenburg RA Alfredsson L Palotie A Peltonen-Palotie L Irwanto A Low HQ Teoh GH Thalamuthu A Kere J D'Amato M Easton DF Nevanlinna H Liu J Czene K Hall P 《Breast cancer research : BCR》2010,12(6):R93-17
Introduction
Breast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In this study, we focused on identifying genetic markers associated with ER-negative breast cancer risk.Methods
We conducted a genome-wide association analysis of 285,984 single nucleotide polymorphisms (SNPs) genotyped in 617 ER-negative breast cancer cases and 4,583 controls. We also conducted a genome-wide pathway analysis on the discovery dataset using permutation-based tests on pre-defined pathways. The extent of shared polygenic variation between ER-negative and ER-positive breast cancers was assessed by relating risk scores, derived using ER-positive breast cancer samples, to disease state in independent, ER-negative breast cancer cases.Results
Association with ER-negative breast cancer was not validated for any of the five most strongly associated SNPs followed up in independent studies (1,011 ER-negative breast cancer cases, 7,604 controls). However, an excess of small P-values for SNPs with known regulatory functions in cancer-related pathways was found (global P = 0.052). We found no evidence to suggest that ER-negative breast cancer shares a polygenic basis to disease with ER-positive breast cancer.Conclusions
ER-negative breast cancer is a distinct breast cancer subtype that merits independent analyses. Given the clinical importance of this phenotype and the likelihood that genetic effect sizes are small, greater sample sizes and further studies are required to understand the etiology of ER-negative breast cancers. 相似文献992.
993.
994.
Kwak EL Bang YJ Camidge DR Shaw AT Solomon B Maki RG Ou SH Dezube BJ Jänne PA Costa DB Varella-Garcia M Kim WH Lynch TJ Fidias P Stubbs H Engelman JA Sequist LV Tan W Gandhi L Mino-Kenudson M Wei GC Shreeve SM Ratain MJ Settleman J Christensen JG Haber DA Wilner K Salgia R Shapiro GI Clark JW Iafrate AJ 《The New England journal of medicine》2010,363(18):1693-1703
995.
Cardiovascular Risk in Young Finns Study Elovainio M Keltikangas-Järvinen L Pulkki-Råback L Kivimäki M Puttonen S Viikari L Räsänen L Mansikkaniemi K Viikari J Raitakari OT 《Psychological medicine》2006,36(6):797-805
BACKGROUND: We tested the hypothesis that depressive symptoms in healthy young adults would be associated with elevated levels of C-reactive proteins (CRP). METHOD: We studied the association between depressive symptoms and CRP in 1201 young adults, as a part of the on-going population-based Cardiovascular Risk in Young Finns Study. Depressive symptoms were determined by responses to a revised version of Beck's Depression Inventory in 1992 and 2001. CRP and other known cardiac risk factors were measured in 2001. RESULTS: Higher depressive symptomatology in 1992 and in 2001 and their means score were related to higher CRP levels (B's range from 0.24 to 0.21, p < 0.001). These relationships persisted after separate adjustments for various risk factors including sex, age, education, oral contraceptive use, dietary fat, physical activity, alcohol consumption, smoking status, LDL-cholesterol, HDL-cholesterol, systolic blood pressure and history of acute infectious disease. Adjustments for obesity and triglycerides levels, however, somewhat attenuated the relationship between depressive symptoms and CRP. CONCLUSIONS: We concluded that higher levels of depressive symptoms are associated with higher levels of CRP, but this association may largely be attributable to obesity or triglycerides. 相似文献
996.
Intense search has been going on to find factors responsible for the asthma and atopy epidemic in Western societies. Attention has increasingly been devoted to environmental saprophytes, which, in addition to gut commensals, might be the major players in the development and fine tuning of immunologic homeostasis. This review outlines current evidence for the role of environmental saprophytes in the development of atopic disease and considers the consequences of urbanization in reducing contacts with soil microorganisms. The major microbial components that have been shown to possess immunomodulatory capacity and their respective Toll-like receptors are also discussed, as are the possible mechanisms underlying the ability of saprophytes to confer protection against atopic disease. 相似文献
997.
998.
Objectives
To measure changes in the visual interpretation of the EEG by the human expert for neonatal seizure detection when reducing the number of recording electrodes.Methods
EEGs were recorded from 45 infants admitted to the neonatal intensive care unit (NICU). Three experts annotated seizures in EEG montages derived from 19, 8 and 4 electrodes. Differences between annotations were assessed by comparing intra-montage with inter-montage agreement (K).Results
Three experts annotated 4464 seizures across all infants and montages. The inter-expert agreement was not significantly altered by the number of electrodes in the montage (p?=?0.685, n?=?43). Reducing the number of EEG electrodes altered the seizure annotation for all experts. Agreement between the 19-electrode montage (K19,19?=?0.832) was significantly higher than the agreement between 19 and 8-electrode montages (dK?=?0.114; p?<?0.001, n?=?42) or 19 and 4-electrode montages (dK?=?0.113, p?<?0.001, n?=?43). Seizure burden and number were significantly underestimated by the 4 and 8-electrode montage (p?<?0.001). No significant difference in agreement was found between 8 and 4-electrode montages (dK?=?0.002; p?=?0.07, n?=?42).Conclusions
Reducing the number of EEG electrodes from 19 electrodes resulted in slight but significant changes in seizure detection.Significance
Four-electrode montages for routine EEG monitoring are comparable to eight electrodes for seizure detection in the NICU. 相似文献999.
Reiman M Parkkola R Lapinleimu H Lehtonen L Haataja L;Pipari Study Group 《Pediatric research》2009,65(1):90-96
Preterm infants have smaller cerebral and cerebellar volumes at term compared with term born infants. Perinatal factors leading to the reduction in volumes are not well known. IL-6 -174 and -572 genotypes partly regulate individual immunologic responses and have also been connected with deviant neurologic development in preterm infants. Our hypothesis was that IL-6 -174 and -572 genetic polymorphisms are associated with brain lesions and regional brain volumes in very low birth weight or in very preterm infants. DNA was genotyped for IL-6 -174 and -572 polymorphisms (GG/GC/CC). Study infants (n = 175) were categorized into three groups according to the most pathologic brain finding in ultrasound examinations until term. The brain MRI performed at term was analyzed for regional brain volumes. Analyzed IL-6 genotypes did not show statistically significant association with structural brain lesions. However, IL-6 -174 CC and -572 GG genotypes associated with reduced volume of one brain region, the combined volume of basal ganglia and thalami, both in univariate and in multivariate analyses (p = 0.009, 0.009, respectively). The association of IL-6 -174 and -572 genetic polymorphisms with smaller volumes in deep gray matter provides us new ways to understand the processes leading to neurologic impairments in preterm infants. 相似文献
1000.
Johannes S Kern Stefan Loeckermann Anja Fritsch Ingrid Hausser Wera Roth Thomas M Magin Claudia Mack Marcel L M��ller Oliver Paul Patrick Ruther Leena Bruckner-Tuderman 《Molecular therapy》2009,17(9):1605-1615
Here, we report on the first systematic long-term study of fibroblast therapy in a mouse model for recessive dystrophic epidermolysis bullosa (RDEB), a severe skin-blistering disorder caused by loss-of-function of collagen VII. Intradermal injection of wild-type (WT) fibroblasts in >50 mice increased the collagen VII content at the dermal–epidermal junction 3.5- to 4.7-fold. Although the active biosynthesis lasted <28 days, collagen VII remained stable and dramatically improved skin integrity and resistance to mechanical forces for at least 100 days, as measured with a digital 3D-skin sensor for shear forces. Experiments using species-specific antibodies, collagen VII–deficient fibroblasts, gene expression analyses, and cytokine arrays demonstrated that the injected fibroblasts are the major source of newly deposited collagen VII. Apart from transitory mild inflammation, no adverse effects were observed. The cells remained within an area ≤10 mm of the injection site, and did not proliferate, form tumors, or cause fibrosis. Instead, they became gradually apoptotic within 28 days. These data on partial restoration of collagen VII in the skin demonstrate the excellent ratio of clinical effects to biological parameters, support suitability of fibroblast-based therapy approaches for RDEB, and, as a preclinical test, pave way to human clinical trials. 相似文献