全文获取类型
收费全文 | 1383篇 |
免费 | 129篇 |
国内免费 | 22篇 |
专业分类
耳鼻咽喉 | 41篇 |
儿科学 | 62篇 |
妇产科学 | 144篇 |
基础医学 | 164篇 |
口腔科学 | 18篇 |
临床医学 | 116篇 |
内科学 | 255篇 |
皮肤病学 | 7篇 |
神经病学 | 254篇 |
特种医学 | 49篇 |
外科学 | 113篇 |
综合类 | 31篇 |
一般理论 | 1篇 |
预防医学 | 83篇 |
眼科学 | 5篇 |
药学 | 70篇 |
中国医学 | 1篇 |
肿瘤学 | 120篇 |
出版年
2021年 | 14篇 |
2020年 | 8篇 |
2019年 | 20篇 |
2018年 | 19篇 |
2017年 | 12篇 |
2016年 | 18篇 |
2015年 | 24篇 |
2014年 | 44篇 |
2013年 | 42篇 |
2012年 | 47篇 |
2011年 | 61篇 |
2010年 | 45篇 |
2009年 | 38篇 |
2008年 | 55篇 |
2007年 | 67篇 |
2006年 | 66篇 |
2005年 | 71篇 |
2004年 | 54篇 |
2003年 | 64篇 |
2002年 | 69篇 |
2001年 | 65篇 |
2000年 | 58篇 |
1999年 | 53篇 |
1998年 | 34篇 |
1997年 | 33篇 |
1996年 | 34篇 |
1995年 | 21篇 |
1994年 | 23篇 |
1993年 | 17篇 |
1992年 | 30篇 |
1991年 | 54篇 |
1990年 | 32篇 |
1989年 | 27篇 |
1988年 | 20篇 |
1987年 | 27篇 |
1986年 | 27篇 |
1985年 | 17篇 |
1984年 | 10篇 |
1983年 | 14篇 |
1982年 | 10篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 11篇 |
1977年 | 7篇 |
1972年 | 6篇 |
1971年 | 4篇 |
1970年 | 7篇 |
1969年 | 7篇 |
1968年 | 8篇 |
排序方式: 共有1534条查询结果,搜索用时 406 毫秒
1.
6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. 总被引:28,自引:5,他引:23 下载免费PDF全文
BACKGROUND: 6-Mercaptopurine (6-MP) has confirmed short and longterm efficacy in the treatment of IBD. However, the relation between its metabolism, efficacy, and side effects is not well understood. AIMS: To assay 6-MP metabolites and to correlate levels with drug compliance, disease activity, and adverse effects of treatment. PATIENTS: Heparinised blood was obtained prior to daily administration of 6-MP in 25 adolescent Crohn's disease patients (14 ileocolitis, 11 colitis) receiving 1.2 (range 0.4-1.6) mg/kg/day for a mean of 17 (range 4-65) months. METHODS: Erythrocyte free bases 6-thioguanine (6-TG) and 6-methyl-mercaptopurine (6-MMP) were measured (pmol/8 x 10(8) red blood cells) using reverse phase high performance liquid chromatography. RESULTS: Disease activity (modified Harvey-Bradshaw index) improved significantly with 6-MP (p = 0.001). Clinical remission was achieved in 72% of patients, who stopped taking prednisone, or were successfully weaned to a low alternate day dose (< 0.4 mg/kg/OD). Remission correlated well with erythrocyte 6-TG (p < 0.05), but not 6-MMP levels. Neutropenia was associated with 6-MP use (p < 0.005), but did not correlate with erythrocyte 6-MP metabolite levels. One patient refractory to 6-MP had 6-TG, but no measureable 6-MMP production, suggesting deficient thiopurine methyl-transferase activity or poor compliance. 6-MP induced complications (hepatitis, pancreatitis, and marrow suppression) were generally associated with increased 6-MMP levels. CONCLUSIONS: These results suggest that high performance liquid chromatography measurement of erythrocyte 6-MP metabolites may provide a quantitative assessment of patient responsiveness and compliance to treatment. The data support an immunosuppressive role for 6-TG, and potential cytotoxicity of raised 6-MMP levels. 相似文献
2.
E Seidman N LeLeiko M Ament W Berman D Caplan J Evans S Kocoshis A Lake K Motil J Sutphen 《Journal of pediatric gastroenterology and nutrition》1991,12(4):424-438
Malnutrition, characterized by weight loss, growth failure and micronutrient depletion, are prominent features of inflammatory bowel disease (IBD) in the pediatric age group. Accurate evaluation of the patient's nutritional status and appropriate nutritional support, whether enteral or parenteral, constitute integral parts of the management of the growing child with IBD. Over the past two decades, a number of studies have supported the potential use of nutritional therapy to induce remission and to control disease activity in symptomatic Crohn's disease. More recently, preliminary studies on the use of dietary supplements of marine-oil-derived omega-3 fatty acids have also indicated a beneficial effect in IBD patients. In parallel with these clinical trials, scientific research has recently focused on the concept that specific dietary alterations can modulate the immune response. Components of the diet that may have particular relevance to mucosal immunity and the pathogenesis of IBD include polyunsaturated fatty acids, nucleotides, and amino acids such as glutamine and arginine. Future research in the interactions between specific nutrients and the immune system will likely increase our understanding of the causes of IBD, as well as enhance the development of novel nutritional therapies for IBD patients. 相似文献
3.
A Borenstein D S Seidman H Trau H Tsur 《The American journal of the medical sciences》1991,301(4):259-261
A 36-year-old man was treated by radiotherapy for tinea capitis many years before discovery of microcystic adnexal carcinoma (MAC). Because of patient's refusal of any surgical intervention, we were able to follow the natural course of this tumor for 13 years. This case emphasizes the typical slow development of (MAC). The implication of the association of MAC and radiotherapy are discussed. 相似文献
4.
Michael D Seidman Mumtaz J Khan Wen Xue Tang Wayne S Quirk 《Otolaryngology--head and neck surgery》2002,127(3):138-144
OBJECTIVES: Lecithin is a polyunsaturated phosphatidylcholine (PPC), which are high energy functional and structural elements of all biologic membranes. PPC play a rate-limiting role in the activation of numerous membrane-located enzymes, including superoxide dismutase and glutathione, which are important antioxidants protecting cell membranes from damage by reactive oxygen species (ROS). ROS-induced damage to mitochondrial DNA may lead to reduced mitochondrial function in the cochlea and resultant hearing loss. STUDY DESIGN AND SETTING: The effects of lecithin on aging and age-associated hearing loss were studied in rats by measuring hearing sensitivities using auditory brainstem responses (ABR). In addition, mitochondrial function as a measure of aging was assessed by determining mitochondrial membrane potentials using flow cytometry and by amplifying mitochondrial DNA deletions associated with aging. Harlan-Fischer rats aged 18 to 20 months (n = 14) were divided into 2 groups. The experimental group was supplemented orally for 6 months with lecithin, a purified extract of soybean phospholipid (Nutritional Therapeutics, Allendale, NJ). RESULTS: The data obtained were compared with the control group. ABRs were recorded at 2-month intervals and showed significant preservation of hearing sensitivities in the treated subjects. Flow cytometry revealed significantly higher mitochondrial membrane potentials in the treated subjects, suggesting preserved mitochondrial function. Finally, the common aging mitochondrial DNA deletion (mtDNA(4834)) were amplified from brain and cochlear tissue including stria vascularis and auditory nerve. This specific deletion was found significantly less frequent in all tissues in the treated group compared with the controls. CONCLUSION: These experiments support our hypothesis and provide evidence that lecithin may preserve cochlear mitochondrial function and protect hearing loss associated with aging. 相似文献
5.
6.
Nancy J Keuthen Nikos Makris John E Schlerf Brian Martis Cary R Savage Katherine McMullin Larry J Seidman Jeremy D Schmahmann David N Kennedy Steven M Hodge Scott L Rauch 《Neuropsychopharmacology》2007,61(3):374-381
BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. RESULTS: As predicted, significant group differences were reported for CBM raw cortical volumes (p = .008) that survived correction for total brain volume (TBV; p = .037) and head circumference (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p = .008), with smaller volumes associated with more severe TTM symptoms. CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reported for the TTM versus NC groups. 相似文献
7.
William S Kremen Larry J Seidman Stephen V Faraone Ming T Tsuang 《Journal of the International Neuropsychological Society》2003,9(1):79-88
Phonemic and semantic fluency involve the capacity to generate words beginning with particular letters or belonging to particular categories, respectively. The former has been associated with frontal lobe function and the latter with temporoparietal function, but neuroimaging studies indicate overlap of underlying neural networks. Schizophrenia patients may experience disproportionate semantic fluency impairment owing to abnormal semantic organization; however, executive dysfunction in schizophrenia suggests possible disproportionate phonemic fluency impairment. Moreover, little is known about the diagnostic specificity of either verbal fluency deficit to schizophrenia or their stability over time. We examined 83 schizophrenia patients, 15 bipolar disorder patients, and 83 normal controls. Both fluency types were impaired in schizophrenia patients. Schizophrenia patients as a whole manifested disproportionate semantic fluency impairment relative to bipolar disorder patients, but only a subset of schizophrenia patients manifested disproportionate semantic fluency impairment relative to controls. Few characteristics, except to some extent paranoid-nonparanoid subtype, meaningfully differentiated schizophrenia patients with and without this disproportionate impairment. Verbal fluency measures were moderately stable over a 4-year period in schizophrenia patients and controls (.48 < rs < .79). These results mirror a literature that overall suggests a small degree of disproportionate semantic fluency impairment in schizophrenia, but also some heterogeneity in fluency deficits. 相似文献
8.
Summary The sensitivity of the cochlea is dependent upon maintenance of a delicate homeostatic environment. One mechanism which participates in providing this environment is the autoregulation of cochlear blood flow. This autoregulation is ensured through the interaction of sympathetic, peptidergic and hemodynamic mechanisms. The current study demonstrates an adaptation that also participates in cochlear blood flow autoregulation. Specifically, an anterior inferior cerebellar arterial network is described and the relative contributions of each of its vessels to total cochlear blood flow is measured using laser Doppler flowmetry. The results show that each collateral vessel contributes to the blood supply of the cochlea and that reperfusion is accompanied by hyperemia. These findings suggest an adaptation that provides stable blood flow through redundancy and compensatory potential. Additionally, these observations have implications for experimental models of ischemia. 相似文献
9.
Laura Telford Scott H. Seidman Gary D. Paige 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,118(1):115-125
Natural head movements include angular and linear components of motion. Two classes of vestibulo-ocular reflex (VOR), mediated
by the semicircular canals and otoliths (the angular and linear VOR, or AVOR and LVOR, respectively), compensate for head
movements and help maintain binocular fixation on targets in space. In this study, AVOR/LVOR interactions were quantified
during complex head motion over a broad range of fixation distances at a fixed stimulus frequency of 4.0 Hz. Binocular eye
movements were recorded (search-coil technique) in squirrel monkeys while fixation distance (assessed by vergence) was varied
using brief presentations of earth-fixed targets at various distances. Stimuli consisted of rotations around an earth-vertical
axis and therefore always activated the AVOR. Horizontal and vertical AVORs were assessed when the head was centered over
the axis of rotation and oriented upright (UP) and right-side-down (RD), respectively. AVOR gains increased slightly with
increasing vergence in darkness, as expected given the small anterior position of the eyes in the head. Combined AVOR/LVOR
responses were recorded when subjects were displaced eccentrically from the rotation axis. Eccentric rotations activated the
AVOR just as when the head was centered, but added a translational stimulus which generated an LVOR component in response
to interaural (IA) or dorsoventral (DV) tangential accelerations, depending on whether the head was UP or RD, respectively.
When the head was eccentric and facing nose-out, the AVOR and LVOR produced ocular responses in the same plane and direction
(coplanar and synergistic), and response magnitudes increased with increasing vergence. With the head facing nose-in, AVOR
and LVOR response components were oppositely directed (coplanar and antagonistic). The AVOR dominated the response when fixation
distance was far, and phase was compensatory for head rotation. As fixation distance decreased toward the rotation axis, responses
declined to near zero, and when fixation distance approached even closer, the LVOR component dominated and response phase
inverted. The same pattern was observed for both horizontal (head UP) and vertical (head RD) responses. The LVOR was recorded
directly by rotating subjects eccentrically but in the nose-up (NU) orientation. The AVOR then generated torsional responses
to head roll, coexistent with either horizontal or vertical LVOR responses to tangential acceleration when the subject was
oriented head-out or right-side-out, respectively. Only the LVOR response components were modulated by vergence. A vectorial
analysis of AVOR, LVOR, and combined responses supports the conclusion that AVOR and LVOR response components combine linearly
during complex head motion.
Received: 27 February 1997 / Accepted: 18 June 1997 相似文献
10.
Phenotypic diversity in hypertrophic cardiomyopathy 总被引:1,自引:0,他引:1
In recent years, the main focus of human genetic studies on hypertrophic cardiomyopathy (HCM) switched from discovering novel genes and defining disease-causing mutations to studies of mutation distribution in disease populations. Eventually these studies will define genotype-phenotype relationships, which may provide clues to understanding the disease process and help to select the most appropriate treatment strategy. Animal models engineered to recapitulate human disease provide a unique tool to investigate the pathogenic mechanisms and evaluate potential therapies. In this review, we present the spectrum of clinical HCM in the context of the genetic heterogeneity of this common human disease. Recent progress made in understanding molecular pathways that result in cardiac hypertrophy and the factors that modify these processes are discussed. 相似文献