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71.
Recent advances in intestinal iron transport 总被引:2,自引:0,他引:2
Our understanding of intestinal iron absorption and its regulation has expanded enormously in recent years. Dietary iron crosses
the enterocyte brush border membrane through the transporter DMTI after first being reduced by the ferric reductase Dcytb.
The subsequent movement of iron across the basolatera1 membrane and into the circulation is mediated by ferroportin1 in conjunction
with the iron oxidase hephaestin. The activity of ferroportin1 is controlled by the liver-derived peptide hepcidin, and the
expression of hepcidin in turn is influenced by plasma transferrin saturation via a pathway that involves HFE, TfR2, and hemojuvelin.
Future studies investigating how these molecules interact will provide a comprehensive understanding of this essential physiologic
process. 相似文献
72.
What should animal models of depression model? 总被引:7,自引:0,他引:7
In this article, we discuss what animal models of depression should be attempting to 'model'. One must first determine if the goal is to model the regulatory mechanisms by which antidepressant treatments alleviate the various symptoms of depression, or to model the dysregulatory mechanisms underlying the etiology of those symptoms. When modeling the mechanisms of antidepressant effects, a key feature that is often overlooked is the time course required for behavioral efficacy. Even in the clinical literature, there is considerable confusion and inconsistency in defining and identifying 'time of onset' of clinical effect. Although the 'therapeutic lag' may not be as long as has been commonly believed, it does occur. Observable improvement in either global symptomatology or specific symptoms becomes evident after 7-14 days of treatment, and more complete recovery takes considerably longer. Thus, any model addressing potential mechanisms of antidepressant action should exhibit a similar time-dependency. Second, whether attempting to address mechanisms underlying behavioral effects of antidepressants, or the neurobiological substrates underlying the development and manifestation of depression, it is essential to recognize that the syndrome of depression is a diagnostic construct that includes a variety of disparate symptoms, some of which may be related mechanistically, and others that may not be specific to depression, but may cut across categorical diagnostic schemes. Further, it is critical to recognize the close relationship of depression and anxiety. Psychological studies have suggested that the myriad symptoms of depression and anxiety may be subsumed within a more limited number of distinct behavioral dimensions, such as negative affect (neuroticism), positive affect, or physiologic hyperarousal. These dimensions may be related to the functioning of specific neurobiological systems. Thus, rather than trying to recreate or mimic the entire spectrum of symptoms comprising the syndrome of depression, it may be more informative to develop animal models for these behavioral dimensions. Such models may then provide access not only to the neural regulatory mechanisms underlying effective antidepressant treatment, but may also provide clues to the processes underlying the development and manifestation of depression. 相似文献
73.
O'Brien MF Connolly SS Kelly DG O'Brien A Quinlan DM Mulvin DW 《Irish journal of medical science》2004,173(1):23-26
Background Patients with prostate cancer with a pre-operative prostate-specific antigen (PSA) τ;15ng/ml who undergo radical retropubic
prostatectomy (RRP) generally do not have a good outcome, yet may have organ-confined cancer and should be offered the option
of surgery.
Aim To assess the outcome of patients who underwent RRP with a pre-operative PSA ≥ 15ng/ml.
Methods Thirty-four patients, mean pre-operative PSA: 25.46ng/ml (15.03–76.6) and mean Gleason score: 6.4 (5–9) were assessed.
Results Two groups were identified. Group I: 41% (14/34) have no biochemical recurrence to mean follow up of 58 months (30–106).
Mean PSA: 18.8ng/ml (15.03–25.84). Mean Gleason score: 6.1 (5–7). Clinical stage: T1c in 80%. No patient had seminal vesicle
or lymph node involvement. Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease to mean follow
up of 66 months (36–98). Mean PSA: 28.9ng/ml (15.28–76.6). Mean Gleason score: 6.7 (5–9). Clinical stage: T1c in 25%. Eleven
patients had seminal vesicle (8) involvement or positive lymph nodes (3) or both (2).
Conclusion RRP seems feasible in patients whose pre-operative PSA is between 15 and 25ng/ml with stage T1c, Gleason score ≤ 7 and negative
lymph node frozen section. 相似文献
74.
Frazer L 《Environmental health perspectives》2004,112(11):A632-A635
As the 2010 phaseout date for chlorofluorocarbons draws nearer, materials engineers are working to find replacements for these ozone-depleting chemicals in the production of plastics and other products. One team of engineers is focusing on a combination of two low-cost and environmentally benign substances--supercritical carbon dioxide and clay nanoparticles--to meet these needs. The result is a strong yet lightweight alternative that retains all the beneficial qualities of solid plastic. 相似文献
75.
Frazer L 《Environmental health perspectives》2004,112(5):A296-A299
76.
Frazer I 《Expert opinion on pharmacotherapy》2004,5(12):2427-2434
One vaccine designed to prevent cancer by preventing a precursor infection is already in common use, and at least one more is in the latter stages of clinical development. These vaccines are part of a new era of cancer immunoprophylaxis. Several further vaccines are in preclinical and clinical development, targeted at preventing cancer precursor infections, and these should add to our ability to prevent this common human disorder. However, vaccines to prevent cancers not triggered by infection are a more remote prospect, for a variety of reasons. 相似文献
77.
78.
79.
Asphalt exposure enhances neuropeptide levels in sensory neurons projecting to the rat nasal epithelium 总被引:3,自引:0,他引:3
Sikora ER Stone S Tomblyn S Frazer DG Castranova V Dey RD 《Journal of toxicology and environmental health. Part A》2003,66(11):1015-1027
Asphalt fumes have been reported to produce nasal irritation in road workers. Since inhaled irritants can increase substance P (SP) production in airway neurons, the effects of asphalt fumes on SP production in trigeminal ganglia (TG) sensory neurons innervating the nasal mucosa were investigated. The effects of asphalt fumes on nasal mucosal innervation were examined by measuring SP and calcitonin-gene-related peptide (CGRP) levels in rat TG neurons projecting to the nasal epithelium. Female Sprague-Dawley rats were exposed to asphalt fumes at 16.0 +/- 8.1mg /m3 for 5 consecutive days, 3.5 h/d. Inflammatory cells were measured in nasal cavity lavage fluid. SP and CGRP immunoreactivity (IR) was measured in the cell bodies of trigeminal ganglion sensory neurons projecting to the nasal cavity. A significant increase in neutrophils and macrophages was observed after asphalt fume exposure indicating an inflammatory response in the nasal cavity. The percentage of SP-IR neurons increased significantly in the asphalt-exposed rats, and the proportion of CGRP-IR neurons was also elevated following asphalt exposure. These results indicate that exposure to asphalt fumes produces inflammation and increases the levels of SP and CGRP in TG neurons projecting to the nasal epithelium. The findings are consistent with asphalt-induced activation of sensory C-fibers in the nasal cavity. Enhanced sensory neuropeptide release from nerve terminals in the nasal cavity may produce neurogenic inflammation associated with nasal irritation following exposure to asphalt fumes. 相似文献
80.
Young SH Robinson VA Barger M Whitmer M Porter DW Frazer DG Castranova V 《Journal of toxicology and environmental health. Part A》2003,66(1):25-38
1-->3-beta-Glucans, derived from the inner cell wall of yeasts and fungi, are commonly found in indoor air dust samples and have been implicated in organic dust toxic syndrome. In a previous study, it was reported that 1-->3-beta-glucan (zymosan A) induced acute pulmonary inflammation in rats. This study investigates which form of 1-->3-beta-glucans, particulate or soluble, is more potent in inducing pulmonary inflammation. Zymosan A was suspended in 0.25 N NaOH for 30 min, neutralized, dialyzed for 2 d using deionized water, and particulate and soluble fractions were collected. Male Sprague-Dawley rats were exposed via intratracheal instillation to NaOH-soluble or NaOH-insoluble zymosan A. At 18 h postexposure, various indicators of pulmonary response were monitored, including indicators of lung damage, such as serum albumin concentration and lactate dehydrogenase (LDH) activity in acellular bronchoalveolar lavage fluid. Inflammation was characterized by an increase in lavageable polymorphonuclear leukocytes (PMN). Pulmonary irritation (breathing frequency increase) and oxidant production (nitric oxide and chemiluminescence, CL) were also monitored. Exposure to the particulate form of NaOH-treated zymosan produced a significant increase in all these indicators. In contrast, rats exposed to the NaOH-soluble fraction were not markedly affected except for LDH, PMN, and CL. However, these increases were significantly less than with exposure to NaOH-insoluble zymosan. Therefore, results demonstrate that particulate zymosan A is more potent in inducing pulmonary inflammation and damage in rats than the soluble form of this beta-glucan. 相似文献