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Purpose:Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis.Methods:Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared.Results:Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis.Conclusion:The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.  相似文献   
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Inflammation, the body’s primary defensive response system to injury and infection, is triggered by molecular signatures of microbes and tissue injury. These molecules also stimulate specialized sensory neurons, termed nociceptors. Activation of nociceptors mediates inflammation through antidromic release of neuropeptides into infected or injured tissue, producing neurogenic inflammation. Because HMGB1 is an important inflammatory mediator that is synthesized by neurons, we reasoned nociceptor release of HMGB1 might be a component of the neuroinflammatory response. In support of this possibility, we show here that transgenic nociceptors expressing channelrhodopsin-2 (ChR2) directly release HMGB1 in response to light stimulation. Additionally, HMGB1 expression in neurons was silenced by crossing synapsin-Cre (Syn-Cre) mice with floxed HMGB1 mice (HMGB1f/f). When these mice undergo sciatic nerve injury to activate neurogenic inflammation, they are protected from the development of cutaneous inflammation and allodynia as compared to wild-type controls. Syn-Cre/HMGB1fl/fl mice subjected to experimental collagen antibody–induced arthritis, a disease model in which nociceptor-dependent inflammation plays a significant pathological role, are protected from the development of allodynia and joint inflammation. Thus, nociceptor HMGB1 is required to mediate pain and inflammation during sciatic nerve injury and collagen antibody–induced arthritis.

The dual threat of infection and injury exerted a significant influence on the evolution of the mammalian immune and nervous systems. The nervous system detects changes in the environment, generates reflexive responses to those changes, and integrates these responses across space and time to establish adaptive memories of events (1, 2). Sensory neurons, termed nociceptors, innervate tissues subjected to infection and injury and are activated by the molecular products of microbes and tissue injury (36). Nociceptor signaling stimulates reflexive neural circuits to coordinate defensive behavior, including inflammation (39). Reflex neural signaling arising in the brain and spinal cord is capable of integrating divergent stimulating and inhibitory inputs, because neural signaling circuits act in opposition (10, 11). This balance of opposing signals enables fine tuning of physiological responses by smoothing gradients of corrective action in response to a changing environment (12). Evolutionary pressure from infection and injury also molded the mammalian immune system to detect changes in the environment, mobilize coordinated defensive reactions, and establish memory (13). The acute onset of infection and injury produces inflammation, defined by pain, edema, heat, redness, and loss of function mediated by immune cells producing cytokines and other inflammatory mediators (6, 14). Because uninhibited inflammation also causes dangerous shock and lethal tissue injury, homeostatic mechanisms at the intersection of the nervous system and immune system have a fundamental role in health by inhibiting inflammation (1517).The nervous system inhibits inflammation by transmitting antiinflammatory signals in the vagus nerve, which arises in the brainstem and sends efferent projections to the organs (1518). In the inflammatory reflex, signals descend from the brain to the abdominal celiac mesenteric ganglia, the origin of the splenic nerve (19, 20). In the spleen, splenic nerve signals stimulate a subset of T lymphocytes to secrete acetylcholine, which interacts with alpha 7 nicotinic acetylcholine receptors to inhibit macrophage production of TNF and other inflammatory mediators (2123). Detailed mechanistic insight into the neuroscience, functional immunology, and molecular mechanisms of the inflammatory reflex enabled therapeutic trials using vagus nerve stimulation to inhibit inflammation in humans. This strategy to stimulate the inflammatory reflex inhibits cytokine release and suppresses inflammation in patients with inflammatory bowel disease and rheumatoid arthritis (2426). Since evolution selects for reflexively controlled homeostatic systems acting antagonistically, here we reasoned it likely also selected for neural reflex circuits which stimulate inflammation and enhance immunity.High mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein conserved across evolution from archaea to mammals, is a necessary and sufficient mediator of sterile injury- and infection-elicited inflammation and immunity (27, 28). It is passively released by cells undergoing necrosis and secreted by innate immune cells activated by inflammation (27, 29). HMGB1 stimulates inflammation by activating the receptor for advanced glycation end products (RAGE) and Toll-like receptor 2, 4, and 9 (TLR 2, 4, and 9) expressed by many different cell types (3032). Signal transduction via these receptors culminates in increased expression of cytokines, and in recruiting and stimulating monocytes, lymphocytes, and neutrophils. HMGB1 also stimulates dendritic cell maturation and enhances antibody responses to antigen, an important early stage in memory formation (33, 34). Administration of HMGB1 antagonists significantly attenuates the severity of inflammation in preclinical models of sepsis, inflammatory bowel disease, arthritis, and neuroinflammation (31, 32, 35, 36).HMGB1 is expressed in the nervous system in cortical neurons and in nociceptors (3740). In preclinical models of nerve injury, HMGB1 levels are increased in the cell bodies of nociceptors residing in the dorsal root ganglia (DRG) (39, 40). In brain neurons, HMGB1 translocates into the cytoplasm and is released during ischemia (38, 41). Exposure of cortical neurons to ethanol activates HMGB1 release via a mechanism dependent upon NOX2/NLRP1 inflammasome (42). Neuronal HMGB1 expression is also significantly enhanced during nerve injury (39, 43, 44). Because HMGB1 stimulates inflammation, and is expressed by nociceptors, and since nociceptors provide a ubiquitous network of nervous system connectivity to peripheral tissues, we reasoned HMGB1 released by nociceptors is a mechanism of neurogenic inflammation. Here, utilizing neuronal-specific ablation of HMGB1 (Syn-Cre/HMGB1fl/fl mice), we discovered a specific role for neuron-derived HMGB1 in inflammation. Genetic silencing of HMGB1 in neurons attenuates inflammation after sciatic nerve injury and in collagen antibody–induced polyarthritis revealing a previously unexpected, but essential, mechanistic role for neuronal HMGB1 in inflammation.  相似文献   
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Structural failure of mechanical heart valve was a known feature when it was evolving in the 1960s and 1970s. With the advent of pyrolytic carbon and a better design, it is a rare entity with present valves. We report a case of disc fracture leading to acute mitral regurgitation in TTK Chitra heart valve prosthesis (CHVP) (TTK Healthcare Limited, India) heart valve, 6 years after its implantation in mitral position.  相似文献   
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Purpose:The aim of this study was to determine the prevalence of diabetic retinopathy (DR) and its risk factors among diabetic patients in rural and urban West Bengal (WB).Methods:Patients were screened in the physician''s clinic by a team of ophthalmologist, optometrist and counsellor. Demographic details, diabetic control, compliance to eye checkup, awareness regarding diabetic blindness, and visual acuity were recorded using a questionnaire. DR was graded both by indirect ophthalmoscopy and fundus photo taken with a portable fundus camera.Results:A total of 1553 subjects were screened over 39 camps across 14 districts of WB over 17 months. The prevalence of DR was 21.51%, with a significant difference between rural (26.55%) and urban (13.89%) areas (P < 0.01). No significant difference with gender was seen (P = 0.99). Presence and grade of DR were related to age, loss of vision, diabetic age, diabetic control, awareness of diabetic blindness and last eye checkup.Conclusion:This study provides the first major prevalence data from WB, and gives valuable insight regarding modifiable risk factors for DR. It is also the first DR study in India to be conducted in the physician''s clinic. The study results emphasise the need to “fix the missing link” between ophthalmologists and treating physicians to win the battle against DR.  相似文献   
88.
    
Mucormycosis, commonly known as ‘Black Fungus’ which was then a rare fungal infection, has suddenly come to light post the COVID-19- pandemic, more so during the second wave in India. It thus becomes important not only for the medical fraternity but also the general population to build awareness about the same. The present review will focus on the pathophysiology, etiology, outcomes of some case studies, and current treatment methods of mucormycosis infection. Major focus of the current article is on rhino-orbital-cerebral mucormycosis. All the studies included in the present review article was extracted from the PubMed database.  相似文献   
89.
    
Preplaced Aggregate Fibrous Concrete (PAFC) is a newly minted composite that has recently become more popular. The production of PAFC involves two essential processes; first, the fibres and coarse aggregate were filled into the empty framework to form the first layer of a natural skeleton, followed by grout injecting. A cement grout fills the voids in the first layer skeleton with slight compaction. This process is repeated to complete the remaining layers; hence, a type of Functionally-graded Preplaced Aggregate Fibrous Concrete (FPAFC) is obtained. The most recent studies revealed that the literature regarding the high-velocity projectile impact on fibrous concrete is well documented; however, the low-velocity repeated projectile impact on PAFC is still unexplored and needs particular emphasis. This research aims to investigate the FPAFC made with a new type of steel and polypropylene fibres against low-velocity projectile impact to fill this research gap. In the current study, twelve mixes were prepared with mono and hybrid combinations of fibres for pioneering the possible utilization of fibres in FPAFC. The maximum fibre dosage in this study is limited to 2.4%. The projectile impact resistance of FPAFC was assessed in line with penetration depth, front and rear damage surface area, weight loss, damage ratio and failure pattern. Additionally, a simplified analytical model was introduced to compute the ejected composite mass from the tested specimens. The results revealed that the addition of steel fibre in a single layer FPAFC exhibited an increasing compressive strength trend compared to the two/three-layered FPAFC. Furthermore, increasing the dosage of fibre at the bottom and top layers of FPAFC with a hybrid combination alleviates the spalling with an increasing number of impacts. The results from this research offer the reference information for more detailed research and studies of FPAFC under low-velocity projectile impact.  相似文献   
90.
    
This research examined the performance of functionally graded two-stage fibrous concrete (FTSFC) against modified repeated falling-mass impacts. This study led to the concept of creating improved multiphysics model of fibre composites with better impact resistance for potential protective constructions. FTSFC was developed based on the bio-inspiring strength of turtle shells. The excellent impact resistance of FTSFC was accomplished by including a larger quantity of steel and polypropylene fibres in the outer layers. At the same time, one- and two-layered concrete were cast and compared to evaluate the efficiency of three-layered FTSFC. To minimize the dispersed test results, a modified form of the 544 drop-mass impact test was recommended by the American Concrete Institute (ACI). The modification was a knife-edge notched specimen instead of a solid cylindrical specimen without a notch. This modification predefined a crack path and reduced the dispersion of results. Cracking and failure impact numbers, ductility index, and failure mode were the testing criteria. The suggested modification to the ACI impact test decreased the coefficient of variance, showing that the dispersion of test results was reduced significantly. This study led to the concept of creating improved, fibre composites with better impact resistance for potential protective constructions.  相似文献   
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