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991.
992.
Complimentary DNAs for three beta-adrenergic receptors (βARs) were isolated and characterised in the fathead minnow. The encoded proteins of 402 (β1AR), 397 (β2AR) and 434 (β3AR) amino acids were homologous to other vertebrate βARs, and displayed the characteristic seven transmembrane helices of G Protein-coupled receptors. Motifs and amino acids shown to be important for ligand binding were conserved in the fathead minnow receptors. Quantitative RT-PCR revealed the expression of all receptors to be highest in the heart and lowest in the ovary. However, the β1AR was the predominant subtype in the heart (70%), and β3AR the predominant subtype in the ovary (53%). In the brain, β1AR expression was about 200-fold higher than that of β2- and β3AR, whereas in the liver, β2AR expression was about 20-fold and 100-fold higher than β3- and β1AR expression, respectively. Receptor gene expression was modulated by exposure to propranolol (0.001-1 mg/L) for 21 days, but not in a consistent, concentration-related manner. These results show that the fathead minnow has a beta-adrenergic receptor repertoire similar to that of mammals, with the molecular signatures required for ligand binding. An exogenous ligand, the beta-blocker propranolol, is able to alter the expression profile of these receptors, although the functional relevance of such changes remains to be determined. Characterisation of the molecular targets for beta-blockers in fish will aid informed environmental risk assessments of these drugs, which are known to be present in the aquatic environment.  相似文献   
993.
Ang II acting at AT(1)Rs has well documented effects on cardiovascular structure such as the promotion of cardiovascular hypertrophy and fibrosis, effects which are believed to be opposed by AT(2)R stimulation. AT(1) and AT(2)R expression are up regulated in senescent hearts, and other components of the local renin-angiotensin system are also dramatically increased in the ageing heart. Therefore, the aim of this study was to determine the role of the AT(2)R in aged rats by determining their potential contribution to the chronic antihypertensive and cardiovascular effects of AT(1)R blockade. Radiotelemetry probes were implanted into senescent (20 months) male Wistar-Kyoto (WKY) rats, and baseline recordings of mean arterial pressure (MAP) were made for 1 week. Candesartan cilexetil (2 mg/kg per day) was given in drinking water, while an additional group simultaneously received the AT(2)R antagonist, PD123319 (10 mg/kg per day) via osmotic mini-pump. At the end of the 4 weeks treatment period, animals were perfusion-fixed to enable histological analysis of cardiovascular structure. MAP was decreased by candesartan cilexetil, however, this effect was not further influenced by PD123319. Cardiac hypertrophy and fibrosis, and aortic hypertrophy were all significantly reduced by candesartan cilexetil. Most interestingly, these structural changes were reversed by concomitant PD123319 administration, despite the lack of AT(2)R-mediated effects on MAP. These results suggest that the AT(2)R does not exert a significant influence on chronic blood pressure regulation in senescent rats. However, PD123319 did reverse AT(1)R-mediated regression of cardiovascular hypertrophy and fibrosis, highlighting the important role of the AT(2)R on cardiovascular structure in the ageing heart and vasculature.  相似文献   
994.
We investigated the emergence of cytomegalovirus (CMV) ganciclovir-resistance mutations in 301 high-risk solid-organ transplant (SOT) recipients after oral prophylaxis, for 100 days, with either valganciclovir or ganciclovir. For patients treated with ganciclovir, the incidence of CMV UL97 mutations was 1.9% (2/103) at the end of prophylaxis and 6.1% (2/33) for patients with suspected CMV disease up to 1 year after transplantation. No resistance mutations were detected in samples from valganciclovir-treated patients. Dual polymerase (UL54) and UL97 resistance mutations were not seen. Valganciclovir was associated with negligible risk of resistance and thus constitutes a useful alternative to ganciclovir prophylaxis for CMV in high-risk SOT recipients.  相似文献   
995.
Lung epithelial progenitor cells: lessons from development   总被引:1,自引:0,他引:1  
The current enthusiasm for stem cell research stems from the hope that damaged or diseased tissues may one day be repaired through the manipulation of endogenous or exogenous stem cells. The postnatal human respiratory system is highly accessible and provides unique opportunities for the application of such techniques. Several putative adult lung epithelial stem cells have been identified in the mouse model system. However, their in vivo capabilities to contribute to different lineages, and their control mechanisms, remain unclear. If stem cell-based therapies are to be successful in the lung, it is vitally important that we understand the normal behavior of adult lung stem cells, and how this is regulated. Lung embryonic progenitor cells are much better defined and characterized than their adult counterparts. Moreover, experiments on a variety of developing tissues are beginning to uncover general mechanisms by which embryonic progenitors influence final organ size and structure. This provides a framework for the study of lung embryonic progenitor cells, facilitating experimental design and interpretation. A similar approach to investigating adult lung stem cells could produce rapid advances in the field.  相似文献   
996.
Purpose: To determine the frequency of intraductal papillary mucinous neoplasm (IPMN) in patients with and without invasive ductal adenocarcinoma (IDAC). Methods: 82 patients underwent pancreatectomy for pancreas adenocarcinoma. 68/82 subjects underwent at least one preoperative imaging study including CT (n = 43), MRI (n = 25), or both (n = 12). Imaging studies were retrospectively evaluated to determine if IPMN was present in the gland at a location distant from IDAC. In 183 different adult patients undergoing MRI for renal mass, images were evaluated to determine the frequency of IPMN. Fisher's exact test was used to test whether the prevalence of IPMN was greater among patients with pancreas cancer than those without. Results: Five of 68 (7.3%) patients who underwent pancreatic resection for IDAC had IPMN at a site distant from the cancer. Two of 182 (1.1%) patients undergoing MRI for renal cancer had imaging evidence of IPMN. There was a significant difference (p = 0.017) in the prevalence of IPMN between patients with and without IDAC. The odds ratio for IPMN as a predictor of pancreas cancer was estimated as 7.18. Conclusion: IPMN occurs with increased frequency in patients with pancreas cancer as opposed to those without pancreas cancer.  相似文献   
997.
In the kidney, the actions of vasopressin on its type-2 receptor (V2R) induce increased water reabsorption alongside polyphosphorylation and membrane targeting of the water channel aquaporin-2 (AQP2). Loss-of-function mutations in the V2R cause X-linked nephrogenic diabetes insipidus. Treatment of this condition would require bypassing the V2R to increase AQP2 membrane targeting, but currently no specific pharmacological therapy is available. The present study examined specific E-prostanoid receptors for this purpose. In vitro, prostaglandin E2 (PGE2) and selective agonists for the E-prostanoid receptors EP2 (butaprost) or EP4 (CAY10580) all increased trafficking and ser-264 phosphorylation of AQP2 in Madin-Darby canine kidney cells. Only PGE2 and butaprost increased cAMP and ser-269 phosphorylation of AQP2. Ex vivo, PGE2, butaprost, or CAY10580 increased AQP2 phosphorylation in isolated cortical tubules, whereas PGE2 and butaprost selectively increased AQP2 membrane accumulation in kidney slices. In vivo, a V2R antagonist caused a severe urinary concentrating defect in rats, which was greatly alleviated by treatment with butaprost. In conclusion, EP2 and EP4 agonists increase AQP2 phosphorylation and trafficking, likely through different signaling pathways. Furthermore, EP2 selective agonists can partially compensate for a nonfunctional V2R, providing a rationale for new treatment strategies for hereditary nephrogenic diabetes insipidus.  相似文献   
998.
We explored the perceptions and experiences of those who support a relative or friend with complex regional pain syndrome (CRPS), a chronic pain condition of unknown aetiology usually affecting a single limb. Semi‐structured interviews were analysed using interpretative phenomenological analysis, and four superordinate themes are presented here. These themes describe the efforts of carers to make sense of CRPS and the rehabilitation process, to be sensitive to the discomfort of the person with CRPS and to respond in an attuned and helpful way. CRPS had become integrated into the carers' lives as they sought to monitor, protect and motivate the person they supported. The themes are discussed in relation to each other and to extant literature, including work on social support and adjustment to chronic illness, and the clinical implications are explored. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   
999.
The use of left ventricular assist devices in treating patients with end-stage heart failure has increased significantly in recent years, both as a bridge to transplantation and as destination therapy in those who are ineligible for cardiac transplantation. This increase is based largely on the results of several recently completed clinical trials with the new second-generation continuous-flow devices that showed significant improvements in survival, functional capacity, and quality of life. Additional information on the use of the first- and second-generation left ventricular assist devices has come from a recently released report spanning the years 2006 to 2009, from the Interagency Registry for Mechanically Assisted Circulatory Support, a National Heart, Lung, and Blood Institute-sponsored collaboration between the U.S. Food and Drug Administration, the Centers for Medicare and Medicaid Services, and the scientific community. The authors review the latest clinical trials and data from the registry, with tight integration of the landmark molecular, cellular, and genomic research that accompanies the reverse remodeling of the human heart in response to a left ventricular assist device and functional recovery that has been reported in a subset of these patients.  相似文献   
1000.
The human host defense peptide, LL‐37, is an important player in the first line of defense against invading microorganisms. LL‐37 and its precursor, hCAP18, have been detected in unstimulated whole saliva but no reports showing hCAP18/LL‐37 in isolated, parotid, and/or submandibular/sublingual saliva have been presented. Here, we measured the levels of hCAP18/LL‐37 in human parotid and submandibular/sublingual saliva and investigated the expression of hCAP18/LL‐37 in parotid and submandibular gland tissue. Parotid and submandibular/sublingual saliva was collected from healthy volunteers, and the levels of hCAP18/LL‐37 in saliva were analyzed by dot blot, ELISA, and western blotting. Cellular expression of hCAP18/LL‐37 in human parotid and submandibular glands was investigated by immunohistochemistry. Immunoreactivity for hCAP18/LL‐37 was detected in both parotid and submandibular/sublingual saliva of all individuals. The concentration of hCAP18/LL‐37 was similar in parotid and submandibular/sublingual saliva, and was determined by densitometric scanning of each dot and normalization to the total protein concentration of each sample, and by ELISA. Double immunohistochemistry revealed that intravascular neutrophils of both parotid and submandibular glands express hCAP18/LL‐37. For the first time, we demonstrate hCAP18/LL‐37 in isolated human parotid and submandibular/sublingual saliva and expression of hCAP18/LL‐37 in glandular intravascular neutrophils, indicating that neutrophils of the major salivary glands contribute to the LL‐37 content of whole saliva.  相似文献   
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