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991.
Julia K. Nunes Colleen Woods Terrell Carter Theresa Raphael Merribeth J. Morin Diadier Diallo Didier Leboulleux Sanjay Jain Christian Loucq David C. Kaslow Ashley J. Birkett 《Vaccine》2014
New interventions are needed to reduce morbidity and mortality associated with malaria, as well as to accelerate elimination and eventual eradication. Interventions that can break the cycle of parasite transmission, and prevent its reintroduction, will be of particular importance in achieving the eradication goal. In this regard, vaccines that interrupt malaria transmission (VIMT) have been highlighted as an important intervention, including transmission-blocking vaccines that prevent human-to-mosquito transmission by targeting the sexual, sporogonic, or mosquito stages of the parasite (SSM-VIMT). While the significant potential of this vaccine approach has been appreciated for decades, the development and licensure pathways for vaccines that target transmission and the incidence of infection, as opposed to prevention of clinical malaria disease, remain ill-defined. This article describes the progress made in critical areas since 2010, highlights key challenges that remain, and outlines important next steps to maximize the potential for SSM-VIMTs to contribute to the broader malaria elimination and eradication objectives. 相似文献
992.
Anna Bitner Paweł Zalewski Jacek J. Klawe Mariusz Kozakiewicz Julia L. Newton 《Central European Journal of Medicine》2014,9(1):126-132
Chronic fatigue syndrome (CFS) is characterized by unexplained fatigue lasting for more than 6 months and accompanied by flulike symptoms. It most commonly affects women aged between 30 and 60 years. To date, clear diagnostic criteria allowing for unambiguous diagno-sis of CFS have not been established. We present a case of a 57-year-old woman with chronic fatigue syndrome in order to showcase the symptoms of this condition and propose a diagnos-tic protocol. 相似文献
993.
Julia H. Zavala Lisa Ecklund-Flores Michael M. Myers William P. Fifer 《Developmental psychobiology》2020,62(2):224-231
Researchers have reported associations between fetal sex and heart rate (FHR) and heart rate variability (FHRV) but rarely in the context of fetal behavioral sleep state. We examined differences in measures of fetal autonomic function by sex and sleep state. Fetal abdominal ECG monitoring technology was used to measure FHR and two measures of FHRV—standard deviation of FHR (SD) and beat-to-beat variability (RMSSD). FHR and movement patterns were also recorded with standard Doppler ultrasound monitor technology employed to code sleep states. Data were collected from 82 healthy fetuses ranging from 36 to 39 weeks gestation. A one-way MANOVA showed that FHR was significantly lower and SD was significantly higher for males than females. Independent samples t tests found that these sex differences were only in the active sleep state. There were no significant differences in RMSSD by sex. Repeated measures MANOVA for a subset that exhibited more than one state (N = 22) showed that SD was significantly different by state. RMSSD showed a marginally significant sleep state difference. In conclusion, fetal sex differences in HR and HRV may indicate more mature autonomic functioning in near-term males than females and fetal sleep state can influence abdominal fECG derived measures of FHR and FHRV. 相似文献
994.
Tawfiq Froukh Omar Nafie Sana' A. S. Al Hait Lucia Laugwitz Julia Sommerfeld Marc Sturm Aya Baraghiti Tala Issa Anis Al-Nazer Philipp A. Koch Johannes Hanselmann Beate Kootz Peter Bauer Wael Al-Ameri Rami Abou Jamra Ayman J. Alfrook Moath Hamadallah Linda Sofan Angelika Riess Tobias B. Haack Olaf Riess Rebecca Buchert 《Clinical genetics》2020,97(4):621-627
We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability. 相似文献
995.
Agnès Garcias López Vasileios Bekiaris Katarzyna Müller Luda Julia Hütter Isabel Ulmert Konjit Getachew Muleta Joy Nakawesi Knut Kotarsky Bernard Malissen Meredith O'Keeffe Bernhard Holzmann William Winston Agace Katharina Lahl 《European journal of immunology》2020,50(10):1525-1536
Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches. 相似文献
996.
Adrian B Levine Jason Peng David Farnell Mitchell Nursey Yiping Wang Julia R Naso Hezhen Ren Hossein Farahani Colin Chen Derek Chiu Aline Talhouk Brandon Sheffield Maziar Riazy Philip P Ip Carlos Parra-Herran Anne Mills Naveena Singh Basile Tessier-Cloutier Taylor Salisbury Jonathan Lee Tim Salcudean Steven JM Jones David G Huntsman C Blake Gilks Stephen Yip Ali Bashashati 《The Journal of pathology》2020,252(2):178-188
Deep learning-based computer vision methods have recently made remarkable breakthroughs in the analysis and classification of cancer pathology images. However, there has been relatively little investigation of the utility of deep neural networks to synthesize medical images. In this study, we evaluated the efficacy of generative adversarial networks to synthesize high-resolution pathology images of 10 histological types of cancer, including five cancer types from The Cancer Genome Atlas and the five major histological subtypes of ovarian carcinoma. The quality of these images was assessed using a comprehensive survey of board-certified pathologists (n = 9) and pathology trainees (n = 6). Our results show that the real and synthetic images are classified by histotype with comparable accuracies and the synthetic images are visually indistinguishable from real images. Furthermore, we trained deep convolutional neural networks to diagnose the different cancer types and determined that the synthetic images perform as well as additional real images when used to supplement a small training set. These findings have important applications in proficiency testing of medical practitioners and quality assurance in clinical laboratories. Furthermore, training of computer-aided diagnostic systems can benefit from synthetic images where labeled datasets are limited (e.g. rare cancers). We have created a publicly available website where clinicians and researchers can attempt questions from the image survey ( http://gan.aimlab.ca/ ). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
997.
Patrick L. Jambura Julia Türtscher René Kindlimann Brian Metscher Cathrin Pfaff Sebastian Stumpf Gerhard W. Weber Jürgen Kriwet 《Journal of anatomy》2020,236(5):753-771
During their evolutionary history, modern sharks developed different tooth mineralization patterns that resulted in very distinct histological patterns of the tooth crown (histotypes). To date, three different tooth histotypes have been distinguished: (i) orthodont teeth, which have a central hollow pulp cavity in the crown, encapsulated by a prominent layer of dentine (orthodentine); (ii) pseudoosteodont teeth, which have their pulp cavities secondarily replaced by a dentinal core of porous dentine (osteodentine), encased by orthodentine; and (iii) osteodont teeth, which lack orthodentine and the whole tooth crown of which consists of osteodentine. The aim of the present study was to trace evolutionary trends of tooth mineralization patterns in modern sharks and to find evidence for the presence of phylogenetic or functional signals. High resolution micro-computed tomography images were generated for the teeth of members of all nine extant shark orders and the putative stem group †Synechodontiformes, represented here by three taxa, to examine the tooth histology non-destructively. Pseudoosteodonty is the predominant state among modern sharks and represents unambiguously the plesiomorphic condition. Orthodonty evolved several times independently in modern sharks, while the osteodont tooth histotype is only developed in lamniform sharks. The two shark orders Heterodontiformes and Pristiophoriformes showed highly modified tooth histologies, with Pristiophorus exhibiting a histology only known from batomorphs (i.e. rays and skates), and Heterodontus showing a histological difference between anterior and posterior teeth, indicating a link between its tooth morphology, histology and durophagous lifestyle. The tooth histotype concept has proven to be a useful tool to reflect links between histology, function and its taxonomic value for distinct taxa; however, a high degree of variation, especially in the pseudoosteodont tooth histotype, demonstrates that the current histotype concept is too simplistic to fully resolve these relationships. The vascularization pattern of the dentine might offer new future research pathways for better understanding functional and phylogenetic signals in the tooth histology of modern sharks. 相似文献
998.
Julia Klawohn Nicholas J. Santopetro Alexandria Meyer Greg Hajcak 《Psychophysiology》2020,57(4):e13520
Individuals with current depression show reduced amplitude of the P300 component of the stimulus-locked event-related potential (ERP)—an effect most often examined in oddball tasks. Although imperative stimuli in response-monitoring paradigms (e.g., the flanker task), also elicit a P300, it is unclear whether a blunted P300 can be observed in depression in these tasks. Moreover, the P300 overlaps with the correct-response negativity (CRN) and error-related negativity (ERN), and is similar to the error positivity (Pe)—response-locked ERPs frequently examined in flanker tasks. The current study examined the stimulus-locked P300 and response-monitoring ERPs on error (i.e., ERN, Pe) and correct responses (i.e., CRN) during an arrowhead flanker task in 72 individuals with a current depressive disorder and 42 never depressed healthy individuals. Consistent with findings from oddball tasks, P300 amplitude was reduced among participants with depression. Further, results indicated increased ERN and CRN, and decreased Pe, in depression. However, when the blunted P300 was included in analyses, group differences in response-monitoring ERPs were no longer evident. Accordingly, P300 amplitudes were correlated negatively with the ERN/CRN and positively with Pe in both groups. A blunted P300 in depression can be observed in speeded response tasks, and can produce apparent increases in ERN and CRN due to ERP component overlap. Further, reduced Pe in participants with depression may reflect a reduced P300 to error commission. These data highlight the central role of reduced P300 in clinical depression, and demonstrate that this effect can be observed across both stimulus- and response-locked ERPs in speeded response tasks. 相似文献
999.
Kohei Fukuoka Yasin Mamatjan Scott Ryall Martin Komosa Julie Bennett Michal Zapotocky Julia Keith Sten Myrehaug Lili‐Naz Hazrati Kenneth Aldape Norm Laperriere Eric Bouffet Uri Tabori Cynthia Hawkins 《Brain pathology (Zurich, Switzerland)》2020,30(3):515-523
We performed genome‐wide methylation analysis on 136 pediatric low‐grade gliomas, identifying a unique cluster consisting of three tumors with oligodendroglioma‐like histology, BRAF p.V600E mutations and recurrent whole chromosome gains of 7 and loss of 10. Morphologically, all showed similar features, including a diffusely infiltrative glioma composed of round nuclei with perinuclear halos, a chicken‐wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high‐grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (>10 chromosomes altered), but none showed 1p/19q co‐deletion or IDH1 p.R132H mutation. Hierarchical clustering and t‐stochastic neighbor embedding analyses from DNA methylation data cluster them more closely to previously described pediatric‐type low‐grade gliomas and separate from adult gliomas. These tumors exhibit distinct clinical features; they are temporal lobe lesions occurring in adolescents and young adults with a prolonged history of seizures and all are alive with no recurrence (follow‐up 3.2 to 13.2 years). We encountered another young adult case with quite similar pathological appearance and molecular status except for TERT promoter mutation. Although the series is small, these may represent a new category of IDH wild‐type low‐grade gliomas which may be confused with “molecular GBM.” Further, they highlight the heterogeneity of IDH wild‐type gliomas and the relatively indolent behavior of “pediatric‐type” gliomas. 相似文献
1000.
David Mataix‐Cols Bjarne Hansen Manuel Mattheisen Elinor K. Karlsson Anjen M. Addington Julia Boberg Diana R. Djurfeldt Matthew Halvorsen Paul Lichtenstein Stian Solem Kerstin Lindblad‐Toh Jan Haavik Gerd Kvale Christian Rück James J. Crowley 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2020,183(1):38-50
Obsessive‐compulsive disorder (OCD) is a debilitating psychiatric disorder, yet its etiology is unknown and treatment outcomes could be improved if biological targets could be identified. Unfortunately, genetic findings for OCD are lagging behind other psychiatric disorders. Thus, there is a pressing need to understand the causal mechanisms implicated in OCD in order to improve clinical outcomes and to reduce morbidity and societal costs. Specifically, there is a need for a large‐scale, etiologically informative genetic study integrating genetic and environmental factors that presumably interact to cause the condition. The Nordic countries provide fertile ground for such a study, given their detailed population registers, national healthcare systems and active specialist clinics for OCD. We thus formed the Nordic OCD and Related Disorders Consortium (NORDiC, www.crowleylab.org/nordic ), and with the support of NIMH and the Swedish Research Council, have begun to collect a large, richly phenotyped and genotyped sample of OCD cases. Our specific aims are geared toward answering a number of key questions regarding the biology, etiology, and treatment of OCD. This article describes and discusses the rationale, design, and methodology of NORDiC, including details on clinical measures and planned genomic analyses. 相似文献