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11.
Kobayashi H; Montgomery KT; Bohlander SK; Adra CN; Lim BL; Kucherlapati RS; Donis-Keller H; Holt MS; Le Beau MM; Rowley JD 《Blood》1994,84(10):3473-3482
Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12-13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown. 相似文献
12.
The electronic medical record. A randomized trial of its impact on primary care physicians' initial management of major depression [corrected 总被引:2,自引:0,他引:2
Rollman BL Hanusa BH Gilbert T Lowe HJ Kapoor WN Schulberg HC 《Archives of internal medicine》2001,161(2):189-197
BACKGROUND: Inadequate treatments are reported for depressed patients cared for by primary care physicians (PCPs). Providing feedback and evidence-based treatment recommendations for depression to PCPs via electronic medical record improves the quality of interventions. METHODS: Patients presenting to an urban academically affiliated primary care practice were screened for major depression with the Primary Care Evaluation of Mental Disorders (PRIME-MD). During 20-month period, 212 patients met protocol-eligibility criteria and completed a baseline interview. They were cared for by 16 board-certified internists, who were electronically informed of their patients' diagnoses, and randomized to 1 of 3 methods of exposure to guideline-based advice for treating depression (active, passive, and usual care). Ensuing treatment patterns were assessed by medical chart review and by patient self-report at baseline and 3 months. RESULTS: Median time for PCP response to the electronic message regarding the patient's depression diagnosis was 1 day (range, 1-95 days). Three days after notification, 120 (65%) of 186 PCP responses indicated agreement with the diagnosis, 24 (13%) indicated disagreement, and 42 (23%) indicated uncertainty. Primary care physicians who agreed with the diagnoses sooner were more likely to make a medical chart notation of depression, begin antidepressant medication therapy, or refer to a mental health specialist (P<.001). There were no differences in the agreement rate or treatments provided across guideline exposure conditions. CONCLUSIONS: Electronic feedback of the diagnosis of major depression can affect PCP initial management of the disorder. Further study is necessary to determine whether this strategy, combined with delivery of treatment recommendations, can improve clinical outcomes in routine practice. 相似文献
13.
Distinct variants of erythrocyte protein 4.1 inherited in linkage with elliptocytosis and Rh type in three white families 总被引:5,自引:0,他引:5
Hereditary elliptocytosis is a heterogeneous disorder resulting from defects in the erythrocyte membrane skeleton. Although some cases of elliptocytosis result from defects in spectrin, the specific structural abnormality has yet to be identified in the majority of cases. Protein 4.1 plays an essential role in erythrocyte membrane physiology, and deficiencies have been implicated in only a few rare cases of elliptocytosis. By using 4.1 immunoblots and a 4.1 radioimmunoassay we identified distinct variants of protein 4.1 in 15 elliptocytic members of three US white families with the Rh-linked form of elliptocytosis. Elliptocytic members of family G were heterozygotes for a low-molecular weight (mol wt) 4.1 variant (65,000 to 68,000 daltons; normal, 80,000) inherited in linkage with the Rz phenotype. Elliptocytic members of family C expressed a simple partial deficiency of protein 4.1 (63% of the normal level) that was inherited in linkage with the r phenotype. Elliptocytic members of family N were heterozygotes for a high-mol wt 4.1 variant (100,000 daltons) also inherited in linkage with the r phenotype. These studies indicate that mutant forms of protein 4.1 are not uncommon in elliptocytosis among whites and that different kindreds probably express different mutations. The observed linkage of elliptocytosis and Rh blood type most likely results from the close proximities of the 4.1 gene (site of the mutation) and the Rh gene, which is located nearby on the short arm of chromosome 1. 相似文献
14.
Programmed cell death, also known as apoptosis, is frequently initiated when cells are deprived of specific trophic factors. To investigate if accelerated apoptosis contributes to the pathogenesis of Diamond- Blackfan anemia (DBA), a rare pure red blood cell aplasia of childhood, we studied the effect of erythropoietin (epo) deprivation on erythroid progenitors and precursors from the bone marrow of DBA patients as compared with hematologically normal controls. Apoptosis in response to epo deprivation was evaluated by enumeration of colony-forming unit- erythroid (CFU-E)- and burst-forming unit-erythroid (BFU-E)-derived colonies in plasma clot semisolid culture and by the identification of typical DNA oligosomes by gel electrophoresis from marrow mononuclear cells in liquid culture. In all DBA patients there was a marked decrease in CFU-E- and BFU-E-derived colony formation compared with normal controls at comparable time points of epo deprivation, with a complete loss of CFU-E-derived colonies in semisolid culture by 9 hours of epo deprivation versus 48 hours in controls. The BFU-E-derived colony response to epo deprivation displayed a similar pattern of decrement. Apoptotic changes assessed by the presence of characteristic DNA fragmentation began in the absence of epo deprivation and were readily detected within 3 hours of epo deprivation in DBA cultures versus 9 hours in controls. We conclude that DBA is characterized by accelerated apoptosis as measured by the loss of erythroid progenitor clonogenicity and increased progenitor and precursor DNA fragmentation leading to the formation of characteristic oligosomes, consistent with an intrinsic erythroid-progenitor defect in which increased sensitivity to epo deprivation results in erythroid failure. 相似文献
15.
Angiogenic factors stimulate mast-cell migration 总被引:18,自引:1,他引:18
Mast cells accumulate at sites of angiogenesis. The factor(s) that control mast-cell recruitment at these sites have yet to be defined. We sought to determine if angiogenic factors result in mast-cell chemotaxis. In this study, we observed that platelet-derived growth factor-AB (PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fibroblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell- shaped dose-response curve. Another potent angiogenic factor, platelet- derived endothelial cell growth factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but still functions as a mast cell chemotactic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic factor. A checkerboard analysis confirmed the directional chemotactic response of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic response induced by PD-ECGF. Cross-desensitization of growth-factor-induced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase- inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect. In summary, our findings suggest that factors known to act on endothelial cells and stimulate neovascularization may simultaneously serve to recruit mast cells to these sites. The local accumulation of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions. 相似文献
16.
Rollman BL Herbeck Belnap B Mazumdar S Houck PR He F Alvarez RJ Schulberg HC Reynolds CF McNamara DM 《Journal of cardiac failure》2012,18(3):238-245
BackgroundGiven the association of depression with poorer cardiac outcomes, an American Heart Association Science Advisory has advocated routine screening of cardiac patients for depression using the 2-item Patient Health Questionnaire (PHQ-2) “at a minimum.” However, the prognostic value of the PHQ-2 among HF patients is unknown.Methods and ResultsWe screened hospitalized HF patients (ejection fraction [EF] <40%) that staff suspected may be depressed with the PHQ-2, and then determined vital status at up to 12-months follow-up. At baseline, PHQ-2 depression screen–positive patients (PHQ-2+; n = 371), compared with PHQ-2 screen–negative patients (PHQ-2?; n = 100), were younger (65 vs 70 years) and more likely to report New York Heart Association (NYHA) functional class III/IV than class II symptoms (67% vs. 39%) and lower levels of physical and mental health–related quality of life (all P ≤ .002); they were similar in other characteristics (65% male, 26% mean EF). At 12 months, 20% of PHQ-2+ versus 8% of PHQ-2? patients had died (P = .007) and PHQ-2 status remained associated with both all-cause (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.4–6.7; P = .003) and cardiovascular (HR 2.7, 95% CI 1.1–6.6; P = .03) mortality even after adjustment for age, gender, EF, NYHA functional class, and a variety of other covariates.ConclusionsAmong hospitalized HF patients, a positive PHQ-2 depression screen is associated with an elevated 12-month mortality risk. 相似文献
17.
When faced with the management of the patient on intensive care with acute kidney injury, the clinician has various choices
to consider. The conventional therapy, where appropriate, is renal replacement therapy. This technique used to be relatively
straightforward but now a relative feast of alternatives is available, not least in choice of buffer and anticoagulant. Two
recent studies add to the growing body of literature concerning alternative anticoagulant regimes, and one in particular should
lead to a change in practice for many of us. We also review some new studies on biomarkers in the diagnosis of acute kidney
injury as well as add yet another nail in the coffin for loop diuretics in the therapy of acute kidney injury. 相似文献
18.
19.
The relationship between cognitive appraisal, affect, and catastrophizing in patients with chronic pain. 总被引:2,自引:0,他引:2
David A Jones Gary B Rollman Kevin P White Marilyn L Hill Ralph I Brooke 《The journal of pain》2003,4(5):267-277
A study was conducted to clarify the nature of catastrophizing, a construct that is frequently referred to in the chronic pain literature. Information regarding 3 affective experience and 3 affect regulation dimensions was gathered from a heterogeneous sample of 104 chronic pain patients by using a semistructured clinical interview and the Affect Regulation and Experience Q-Sort (AREQ). Self-report questionnaires included visual analog pain scales, the Coping Strategies Questionnaire (CSQ), Multidimensional Pain Inventory (MPI), McGill Pain Questionnaire (MPQ), and Center for Epidemiological Studies Depression scale (CES-D). Hierarchical multiple regression was used to demonstrate the relative contributions of affective and cognitive appraisal components of catastrophizing. Thirty-one percent of the variance in CSQ-Catastrophizing scores was explained by a combination of cognitive appraisal variables (perceived ability to control pain; MPI Life Control) and AREQ scores, even after adjusting for pain severity and chronicity, age, and sex of participants. Results of the study strongly suggest that, rather than thinking of catastrophizing primarily as a cognitive coping construct, it should be described as an elaborate construct made up of both cognitive appraisal and affective components. Implications for tailoring interventions to match individual styles of affect regulation are discussed. 相似文献
20.
Dermatophytosis: fluorostaining enhances speed and sensitivity in direct microscopy of skin,nail and hair specimens from dermatology outpatients 下载免费PDF全文
Direct microscopy of keratinised specimens is a standard screening procedure that assists clinicians to differentiate true superficial mycoses from non‐fungal disorders of the skin, nail and hair. Most clinical dermatologists use bright‐field microscopy when searching for dermatophyte fungi in clinical samples while laboratory‐based mycologists increasingly favour fluorescence microscopy in order to optimise visualisation of fungal elements. This study compared the validity and speediness of fluorescence microscopy vs. conventional light microscopy when screening for fungi in 206 dermatological samples from dermatology outpatients. Both senior dermatologist and a less experienced investigator (medical student) attained high and comparable levels of specificity (91.7–93.8%), positive predictive value (77.1–81.4%) and negative predictive value (83.7–89.9%) using either method. Fluorostaining with Blankophor prior to fluorescence microscopy increased the sensitivity by 22 ± 1% as compared to light microscopy of unstained samples. For both investigators, the time required to identify fungal elements by the fluorescence‐based technique was reduced by at least 50%, thus improving the performance of direct microscopy in the clinical setting. 相似文献