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排序方式: 共有618条查询结果,搜索用时 15 毫秒
81.
Ayelet Rosenthal-Simons Andrea R. Durrant Uriel Heresco-Levy 《European neuropsychopharmacology》2013,23(12):1659-1671
Glutamatergic neurotransmission is mediated via complex receptorial systems including N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) and metabotropic receptor subtypes and plays a critical role in the modulation of synaptic plasticity, mood, cognitive processes and motor behavior. Glutamatergic function deficits are hypothesized to contribute to the pathogenesis of neuropsychiatric disorders, including schizophrenia, mood and movement disorders. Accumulating data are rapidly leading to the characterization of specific types of autoimmune encephalitis in which the receptors and proteins critically involved in glutamatergic neurotransmission, e.g., NMDA, AMPA receptors, are antigen targets. Characteristic of these syndromes, antibodies alter the structure and/or function of the corresponding neuronal antigen resulting in clinical pictures that resemble pharmacological disease models. Presently the best characterized autoimmune glutamatergic disorder is anti-NMDA receptor encephalitis. This disorder manifests with intertwined psychiatric and neurological features, defines a new syndrome, reclassifies poorly defined clinical states and extends previous hypotheses, such as hypo-NMDA receptor function in schizophrenia. The characterization of autoimmune-induced glutamatergic receptor dysfunctions (AGRD) is likely to have a substantial conceptual impact upon our understanding of neuropsychiatric disorders including schizophrenia, affective and movement dysfunctions. Further definition of AGRD will provide additional guidelines for psychiatric diagnoses, identification of homogeneous patient subtypes within broad phenomenological classifications and will contribute to the development of personalized treatments. The body of knowledge already accumulated on anti-NMDA receptor encephalitis highlights the need for wide dissemination of these concepts among psychiatrists, and in suspected cases, for early recognition, prompt clinical and laboratory investigation and efficient interface between mental health and medical teams. 相似文献
82.
Nagamani SC Erez A Bay C Pettigrew A Lalani SR Herman K Graham BH Nowaczyk MJ Proud M Craigen WJ Hopkins B Kozel B Plunkett K Hixson P Stankiewicz P Patel A Cheung SW 《European journal of human genetics : EJHG》2012,20(2):176-179
Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion. 相似文献
83.
Understanding the mechanoresponsiveness of adipocytes and the characteristics of the mechanical stimuli that regulate adipogenesis
is critically important in establishing knowledge in regard to the long-term effects of a sedentary lifestyle (or immobility
in extreme medical conditions) as well as concerning obesity and related diseases. In this study we subjected 3T3-L1 preadipocytes
cultured on elastic substrata to different levels of static equiaxial tensile strains within the physiological range, up to
substrate tensile strain (STS) of 12%, while inducing differentiation in the cultures. Based on prior work which revealed
that adipogenesis is accelerated in cultures subjected to STS of 12% by activating the mitogen-activated protein kinase kinase
signaling pathway, we were specifically interested in identifying the STS levels which trigger this process. We hence monitored
the production and accumulation of lipid droplets (LDs) using a non-destructive, image-processing-based method that we have
previously developed, for a period of 4 weeks. The experimental data demonstrated accelerated adipogenesis in the cultures
subjected to STS levels of 6%, 9%, and 12% with respect to cultures subjected to STS of 3% and (non-stretched) control cultures.
This accelerated adipogenic response to the large sustained STS manifested in significantly larger numbers and greater sizes
of LDs in the cultures that were stretched to large STS levels (p < 0.05), starting at approximately day 14 following induction of differentiation. Hence, indeed, there appears to be a certain
tensile strain threshold, or domain—which is found within the physiological range—above which the responsiveness of adipocytes
to sustained static stretching increases and is manifested in accelerated adipogenesis. 相似文献
84.
Halevy A Basel-Vanagaite L Shuper A Helman S Har-Zahav A Birk E Maya I Kornreich L Inbar D Nürnberg G Nürnberg P Steinberg T Straussberg R 《Pediatric neurology》2012,46(6):363-368
Postnatal microcephaly is defined as normal head circumference at birth, which progressively declines to more than 2 standard deviations below the average for the patient's age and sex. We describe four patients from three consanguineous families of Arab Bedouin origin who presented with autosomal recessive inheritance of progressive microcephaly, spasticity, thin corpus callosum, pyramidal signs, and intellectual disability. Homozygosity mapping (Human Mapping NspI 250K arrays, Affymetrix, Santa Clara, CA) placed the disease locus at 8q23.2-q24.12. The candidate region includes 22 known or predicted genes, including RAD21, which is related to the cohesion complex EIF3H, which is involved in translation initiation, and TAF2, which may be involved in intellectual disability. Identification of the causative gene in our reported family will shed light on the pathogenesis of this severe condition. 相似文献
85.
Shorer Y Biderman A Levy A Rabin S Karni A Maoz B Matalon A 《Annals of family medicine》2011,9(6):549-551
The cornerstone of family medicine is the belief in both the continuity and availability of care. These beliefs are challenged when a doctor leaves his or her clinic because of personal reasons. In the example described in this article, the involvement of colleagues in a Balint group led a doctor to a flash insight into her conflicting feelings related to leaving her clinic. The group process helped her to prepare and deal with her own feelings and needs, as well as those of her patients and staff. Balint groups are a secure place to explore and gain insight into the emotional aspects of attachment and separation of physicians from their patients. 相似文献
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89.
The contribution of a directional preference of stiffness to the efficacy of prophylactic sacral dressings in protecting healthy and diabetic tissues from pressure injury: computational modelling studies 下载免费PDF全文
The sacral region is the most common site for pressure injuries (PIs) associated with lying in bed, and such sacral PIs often commence as deep tissue injuries (DTIs) that later present as open wounds. In complex patients, diabetes is common. Because, among other factors, diabetes affects connective tissue stiffness properties, making these tissues less able to dissipate mechanical loads through physiological deformations, diabetes is an additional biomechanical risk factor for PIs and DTIs. A preventive measure with established successful clinical outcomes is the use of sacral prophylactic dressings. The objective of this study has been to expand our previous work regarding the modes of action and biomechanical efficacy of prophylactic dressings in protecting the soft tissues adjacent to the sacrum by specifically examining the role of a directional stiffness preference (anisotropy) of the dressing while further accounting for diabetic tissue conditions. Multiple three‐dimensional anatomically detailed finite element (FE) model variants representing diabetic tissue conditions were used, and tissue loading state data were compared with healthy tissue simulations. We specifically compared soft tissue exposures to elevated internal shear stresses and strain energy densities (SED) near the sacrum during supine weight bearing on a standard (foam) hospital mattress without a dressing, with a prophylactic dressing lacking directional stiffness preferences and with an anisotropic dressing. Our results have clearly shown that an anisotropic dressing design reduces the peak tissue stresses and exposure to sustained tissue deformations in both healthy and diabetic cases. The present study provides additional important insights regarding the optimal structural and material design of prophylactic dressings, which in turn, informs clinicians and decision makers regarding beneficial features. 相似文献
90.