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991.
The aim of this investigation is to estimate the contribution of spatial glial K+ buffer currents to extracellular K+ homeostasis during enhanced neuronal activity. Neuronal hyperactivity was induced by electrical stimulation of the cortical surface or the ventrobasal thalamic nuclei of cats (5-50 Hz, 0.1-0.2 ms, two to three times threshold stimulation intensity, 5-20 s). The accompanying slow field potential changes were recorded simultaneously across the grey matter with vertical assemblies of eight micropipettes glued 300 microns apart. Using the Poisson equation, the amplitudes of the underlying current sources and sinks were calculated. The current source densities depended on the depth of recording, frequency, strength, and duration of the stimulation. Current sinks, corresponding to a removal of 0.1-0.5 mmoles of monovalent cations per liter of brain tissue and second from the extracellular space, were observed in middle cortical layers, whereas sources appeared at superficial and deeper sites. These sinks and sources might represent K+ moved across glial membranes by spatial buffer currents. The consequences of glial buffer currents of this magnitude were investigated with model calculations. It turned out that measurements of electrolyte and volume changes of the extracellular space (Dietzel et al. Exp. Brain Res. 40:432-439, 1980; Exp. Brain Res. 46:73-84, 1982) could only partially be explained by spatial buffer currents of this magnitude. Comparison of the calculated values with intracellular measurements in neurons and glial cells (Coles et al. Ann. N.Y. Acad. Sci. 481:303-317, 1986; Ballanyi et al. J. Physiol. 382:159-174, 1987) suggests that spatial buffering combines with an approximately equimolar KCl transport and, depending on the preparation, also K+/Na+-exchange across glial membranes. 相似文献
992.
Adrián Abalovich Carlos Wechsler Silvia Lara Miguel Bervottini 《Xenotransplantation》2010,17(4):263-266
Abalovich A, Wechsler C, Lara S, Bervottini M. Pig islet xenotransplantation acceptance in a Latin‐American diabetic population. Xenotransplantation 2010; 17: 263–266. © 2010 John Wiley & Sons A/S. Abstract: Progress in porcine islet xenotransplantation has been accompanied by studies on acceptance of this new procedure by patients, health professionals or the general public. Such studies have not been done in the Latin‐American population. We conducted a questionnaire in 108 diabetes patients (insulin‐dependent, n = 53; insulin‐independent, n = 55) in a public hospital in Argentina. The questions addressed the general perception of the xenotransplant procedure and specific items related to the outcome (achieving insulin independence, improvement in metabolic control, delay in emergence of diabetic complications, need for repeat procedures, potential of transfer of infectious viruses, association with psychological problems, and anticipated success in relation to achieving a cure). Eighty‐six (79%) of the patients accepted islet xenotransplantation; this incidence was not different for insulin‐dependent or insulin‐independent patients, patients with or without complications, or patients with good or poor metabolic control. Also, over 75% of patients accepted the procedure if this is only associated with a reduction in insulin requirement, if the procedure just delays but not prevents the onset of complications, or if the procedure needs to be performed every 6 months. Fifty‐seven percent of patients indicated acceptance even if the potential transmission of a virus infection cannot be completely ruled out: this outcome was not affected by the outbreak of the H1N1 flu epidemic during the conduct of this study. Forty percent of patients indicated that living with porcine cells in their body could give psychological problems. We conclude that this population of Latin‐American diabetic patients shows a high acceptance rate of a porcine islet xenotransplantation product. 相似文献
993.
David G. Stevenson PhD Vincent Mor PhD 《Journal of the American Geriatrics Society》2009,57(9):1678-1684
In the Quality Improvement Organization (QIO) program's latest Statement of Work, the Centers for Medicare and Medicaid Services (CMS) is targeting its nursing home activities toward facilities that perform poorly on two quality measures—pressure ulcers and restraint use. The designation of target facilities is a shift in strategy for CMS and a direct response to criticism that QIO program resources were not being targeted effectively to facilities or clinical areas that most needed improvement. Using administrative data, this article analyzes implications of using narrowly defined criteria to identify facilities that need improvement, particularly in light of considerable evidence showing that nursing home quality is multidimensional and may change over time. The analyses show that one in four facilities is targeted for improvement nationally but that approximately half of some states' facilities are targeted while other states have almost none targeted. The analyses also convey deeper limitations to using threshold values on individual measures to identify poorly performing homes. Target facilities can be among the top performers on a range of other quality measures, and their performance on targeted measures themselves may change over time. The implication of these features is that a very different group of facilities would have been chosen had the QIO program targeted other measures or examined performance at a different point in time. Ultimately, CMS has chosen a blunt instrument to identify poorly performing nursing homes, and supplemental strategies—such as soliciting input from state survey agencies and more closely aligning quality improvement and quality assurance efforts—should be considered to address potential limitations. 相似文献
994.
995.
Jürgen Kleine-Vehn Johannes Leitner Marta Zwiewka Michael Sauer Lindy Abas Christian Luschnig Ji?í Friml 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(46):17812-17817
All eukaryotic cells present at the cell surface a specific set of plasma membrane proteins that modulate responses to internal and external cues and whose activity is also regulated by protein degradation. We characterized the lytic vacuole-dependent degradation of membrane proteins in Arabidopsis thaliana by means of in vivo visualization of vacuolar targeting combined with quantitative protein analysis. We show that the vacuolar targeting pathway is used by multiple cargos including PIN-FORMED (PIN) efflux carriers for the phytohormone auxin. In vivo visualization of PIN2 vacuolar targeting revealed its differential degradation in response to environmental signals, such as gravity. In contrast to polar PIN delivery to the basal plasma membrane, which depends on the vesicle trafficking regulator ARF-GEF GNOM, PIN sorting to the lytic vacuolar pathway requires additional brefeldin A-sensitive ARF-GEF activity. Furthermore, we identified putative retromer components SORTING NEXIN1 (SNX1) and VACUOLAR PROTEIN SORTING29 (VPS29) as important factors in this pathway and propose that the retromer complex acts to retrieve PIN proteins from a late/pre-vacuolar compartment back to the recycling pathways. Our data suggest that ARF GEF- and retromer-dependent processes regulate PIN sorting to the vacuole in an antagonistic manner and illustrate instrumentalization of this mechanism for fine-tuning the auxin fluxes during gravitropic response. 相似文献
996.
Marco Minoia Muriel Gaillard Friedrich Reinhard Milos Stojanov Vladimir Sentchilo Jan Roelof van der Meer 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(52):20792-20797
Genomic islands (GEI) comprise a recently recognized large family of potentially mobile DNA elements and play an important role in the rapid differentiation and adaptation of bacteria. Most importantly, GEIs have been implicated in the acquisition of virulence factors, antibiotic resistances or toxic compound metabolism. Despite detailed information on coding capacities of GEIs, little is known about the regulatory decisions in individual cells controlling GEI transfer. Here, we show how self-transfer of ICEclc, a GEI in Pseudomonas knackmussii B13 is controlled by a series of stochastic processes, the result of which is that only a few percent of cells in a population will excise ICEclc and launch transfer. Stochastic processes have been implicated before in producing bistable phenotypic transitions, such as sporulation and competence development, but never before in horizontal gene transfer (HGT). Bistability is instigated during stationary phase at the level of expression of an activator protein InrR that lays encoded on ICEclc, and then faithfully propagated to a bistable expression of the IntB13 integrase, the enzyme responsible for excision and integration of the ICEclc. Our results demonstrate how GEI of a very widespread family are likely to control their transfer rates. Furthermore, they help to explain why HGT is typically confined to few members within a population of cells. The finding that, despite apparent stochasticity, HGT rates can be modulated by external environmental conditions provides an explanation as to why selective conditions can promote DNA exchange. 相似文献
997.
998.
999.
D. R. Saban S. K. Chauhan X. Zhang J. El Annan Y. Jin R. Dana 《American journal of transplantation》2009,9(3):473-482
Certain components of a graft that provoke alloimmunity may not be vital for graft function or critical as targets of rejection. Corneal transplantation is an example of this, because graft epithelium plays a role in allosensitization, whereas corneal graft endothelium—which shares the same alloantigens—is the critical target in allorejection. In this study, we found that exploiting this biology by replacing donor epithelium of an allograft with an allodisparate third-party epithelium yields a marked enhancement in transplant survival. Such 'chimeric' allografts consisted of a C3H/He (H-2k ) corneal epithelium over a C57BL/6 (H-2b ) epithelial-denuded cornea (or v.v. ) and orthotopically placed on BALB/c (H-2d ) hosts. Conventional corneal allografts (C3H/He or C57BL/6) or isografts (BALB/c) were also transplanted on BALB/c hosts. Alloreactive T-cell frequencies (CD4+ interferon [IFN]-γ+ ) primed to the graft endothelium were strongly diminished in chimeric hosts relative to conventionally allografted hosts. This was corroborated by a decreased T-cell infiltration (p = 0.03) and a marked enhancement of allograft survival (p = 0.001). Our results represent the first successful demonstration of chimeric tissue, epithelial-denuded allograft plus third-party allodisparate epithelium, in the promotion of allograft survival. Moreover, chimeric grafting can be readily performed clinically, whereby corneal allograft rejection remains a significant problem particularly in inflamed graft beds. 相似文献
1000.
疼痛治疗目前仍主要依赖阿片药物,但阿片药物的耐药性给病人增加了极大的痛苦,严重影响了阿片药物的应用。目前的研究结果表明,阿片耐药的产生分为系统内和系统间两种机制。本文仅从阿片受体的系统内调节的角度,对阿片耐药的机制进行阐述,总结系统内调节机制的研究进展和热点问题。 相似文献