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31.
John S Thompson Claire Pomeroy Richard J Kryscio Stephen A Brown Donna Reece Rita Kramer Dianna S Howard Gary VanZant Suzanne Humphries Gordon Phillips 《Biology of blood and marrow transplantation》2004,10(12):858-866
To reduce the toxicity of traditional conditioning regimens for allogeneic stem cell transplantation (allo-SCT), we used single-agent chemotherapy conditioning with either busulfan (total cumulative dose, 16 mg/kg) or melphalan (200 to 240 mg/m 2 ), followed by the anti-T cell-specific monoclonal antibody T10B9 (MEDI-500) daily for 3 days. T cell-replete SCT was performed from HLA-identical sibling donors. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of 7 additional days of T10B9 and delayed onset of cyclosporine (ie, on day +4 or +5). Twenty-six high-risk hematologic malignancy patients were entered onto this study. All 24 patients who survived longer than 8 days engrafted, although 1 patient experienced late graft failure. Deaths occurred in 21 of 26 patients because of infection (n = 7), progression/recurrence of primary disease (n = 6), aGVHD (n = 4), regimen-related toxicity (n = 1), and other causes (n = 3). Five of these patients are enjoying disease-free survival with a median survival of 1193 days after allo-SCT. The conditioning regimen induced modulation of surface expression of CD3 (but not CD4 or CD8) and was associated with decreasing tumor necrosis factor-alpha (but not interleukin-6) serum levels. In conclusion, single-agent chemotherapy conditioning with T10B9 produced durable engraftment and long-term survival in some patients who would not have qualified for a traditional allo-SCT. 相似文献
32.
CD1a and antitumour immune response 总被引:3,自引:0,他引:3
Primary immune response is based on the capacity of local professional antigen-presenting cells (whose prototype is represented by dendritic cells, DCs) to take up and present antigens to selected clones of T cells, but also to non-specific effector cells such as macrophages or natural killer cells. The four CD1 proteins, all of which share a limited homology to class I MHC proteins, are differently expressed in various cell types, of both mesenchymal and, as recently described, epithelial lineage. Regarding the role of CD1 molecules in the anti-tumour response, it has been reported that CD1+ dendritic cells are involved in the first steps of the primary immune response in a number of malignancies. Moreover, the presence of a high number of DCs in the tumoral or peritumoral area, as well as in the draining lymph nodes, has been shown to correlate with a better prognosis. A recent report on the presence of CD1a in metaplastic epithelial cells of Barrett esophagus introduced new questions about CD1a expression patterns. Moreover, the strong correlation between the lack of CD1a+ cells and the malignant evolution of the lesion may indicate a possible role of non-professional APCs in mediating and/or potentiating immune responses to tumours. 相似文献
33.
34.
Cyclin alterations in giant cell tumor of bone. 总被引:3,自引:0,他引:3
Adel Kauzman Shu Qiu Li Grace Bradley Robert S Bell Jay S Wunder Rita Kandel 《Modern pathology》2003,16(3):210-218
Cyclins play an important role in regulating the passage of dividing cells through critical checkpoints in the cell cycle. Because alterations of several cyclins, especially cyclin D1, have been implicated in the development of many human neoplasms, we examined 32 cases of giant cell tumor of long bones for cyclin D1 gene amplification and protein overexpression using differential polymerase chain reaction and immunohistochemistry, respectively. In addition, the expression of cyclin D3, cyclin B1, and the proliferation-associated antigen Ki-67 (MIB-1) was assessed immunohistochemically. Low-level cyclin D1 gene amplification was detected in 61% of giant cell tumor cases. All tumors showed cyclin D1, cyclin D3, cyclin B1, and Ki-67 (MIB-1) staining; however, the distribution was very characteristic. Cyclin D1 protein expression was seen predominantly in the nuclei of the giant cells, with occasional mononuclear cells staining. There was no correlation between cyclin D1 gene amplification and protein overexpression. Cyclin D3 staining showed a similar distribution, with 88% of cases showing protein overexpression. Cyclin D1 and/or D3 staining in the giant cells was never associated with staining for either cyclin B1 or Ki-67 (MIB-1), as the expression of the latter two proteins was restricted to the mononuclear cells. Cyclin B1 overexpression was seen in 44% of cases. Ki-67 (MIB-1) staining was present in all cases, and between 10 to 50% of the mononuclear cells were positive. These results suggest that alterations in cyclin D1 and/or D3 might play a role in the pathogenesis of giant cell tumor of bone. 相似文献
35.
Overexpression of connexin43 alters the mutant phenotype of midgestational wnt-1 null mice resulting in recovery of the midbrain and cerebellum 总被引:1,自引:0,他引:1
Melloy PG Kusnierczyk MK Meyer RA Lo CW Desmond ME 《The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology》2005,283(1):224-238
The midbrain-hindbrain (MHB) junction plays a key role in the patterning of the embryonic neural tube and the formation of brain structures such as the cerebellum. The mitogen wnt-1 is critical for cerebellar development, as evidenced by the lack of MHB region and cerebellar formation in the wnt-1 null embryo. We have generated wnt-1 null embryos overexpressing the gap junction gene connexin43 by crossing wnt-1 null heterozygotes into the CMV43 mouse line. We have confirmed that these mice show an increase in gap junctional communication by dye coupling analysis. Two-thirds of wnt-1 null CMV43(+) mouse embryos at E18.5 have a cerebellum. In addition, changes in the wnt-1 null phenotype in mouse embryos overexpressing connexin43 are observed as early as E9.5. At this stage, one-quarter of wnt-1 null CMV43(+) embryos display extra or expanded tissue present at the MHB boundary (a wnt-1 null enlarged phenotype). In situ hybridization studies conducted on these embryos have indicated no changes in the expression of embryonic brain positional markers in this region. We conclude from these studies that overexpression of the connexin43 gap junction restores cerebellar formation by compensating for the loss of wnt-1. 相似文献
36.
Development of nociceptive synaptic inputs to the neonatal rat dorsal horn: glutamate release by capsaicin and menthol 总被引:4,自引:3,他引:4
To study the postnatal development of nociceptive synaptic inputs in the superficial dorsal horn of the neonatal rat spinal cord, we examined the effect of capsaicin and menthol on glutamatergic mEPSCs in postnatal day (P) 0–1, P5–6 and P9–11 slices of spinal cord. Capsaicin (100 n m to 2 μ m ) increased the mEPSC frequency in a concentration-dependent manner at all ages tested, with a significant enhancement of the effect between P5 and P10. This effect was sensitive to vanilloid receptor (VR) antagonists. The elevation in mEPSC frequency occurred at concentrations of capsaicin (100 n m ) that did not alter the distribution of mEPSC amplitudes and was abolished by a dorsal rhizotomy, demonstrating that capsaicin acts via presynaptic VR1 receptors localized on primary afferents. Menthol significantly increased the mEPSC frequency with a similar developmental pattern to capsaicin without consistently affecting mEPSC amplitude. The increase in mEPSC frequency following capsaicin did not depend on transmembrane calcium influx since it persisted in zero [Ca2+ ]o . The facilitation of spontaneous glutamate release by capsaicin was sufficient to evoke action potentials in neonatal dorsal horn neurons but was accompanied by a block of EPSCs evoked by electrical stimulation of the dorsal root. These results indicate that VR1-expressing nociceptive primary afferents form functional synaptic connections in the superficial dorsal horn from birth and that activation of the VR1 receptor increases spontaneous glutamate release via an undetermined mechanism. In addition, the data suggest that immature primary afferents express functional menthol receptors that are capable of modulating transmitter release. These results have important functional implications for infant pain processing. 相似文献
37.
Abrams DI Bebchuk JD Denning ET Davey RT Fox L Lane HC Sampson J Verheggen R Zeh D Markowitz NP;Terry Beirn Community Programs for Clinical Research on AIDS 《Journal of acquired immune deficiency syndromes (1999)》2002,29(3):221-231
The effect of intermittent courses of recombinant interleukin-2 (rIL-2) on HIV-1 load in patients receiving combination antiretroviral therapy remains uncertain. CPCRA 059 was an open-label, randomized, multicenter trial in which 511 patients with HIV-1 infection and CD4+ cell counts of > or = 300/mm3 who were receiving antiretroviral therapy were assigned to receive no rIL-2 (255 patients [controls]) or subcutaneous rIL-2 in dosages of 4.5 MIU (130) or 7.5 MIU (126) twice daily for 5-day courses every 8 weeks to maintain CD4+ cell counts that were twice the baseline value or > or = 1,000/mm3. The primary objective of this study was to compare the effects of the two doses of rIL-2 and no rIL-2 on viral load and CD4+ cell counts over 12 months. There was no difference in the following viral load measurements between the rIL-2 treatment groups and the control treatment group: percentage of patients with viral loads of <50 copies/mL at 12 months (p =.55), time to viral load of > or = 50 copies/mL for patients who had baseline viral loads of <50 copies/mL (p =.35), and change in viral load from baseline for patients who had viral loads of > or = 50 copies/mL at baseline (p =.63). At each follow-up visit, the change in CD4+ cell count from baseline was significantly greater in the rIL-2 treatment groups than in the control treatment group, with a mean difference of 251/mm3 at month 12 (95% confidence interval, 207-295; p <.0001). No unanticipated adverse experiences were seen in this trial, to our knowledge the largest randomized evaluation of rIL-2 treatment conducted to date. 相似文献
38.
Rita Nigam Jian-Ping Jin Christopher R. Triggle 《Journal of muscle research and cell motility》1998,19(6):695-703
To investigate the controversial issue concerning the role of calponin in smooth muscle contraction, this study examined the relationship between smooth muscle calponin and the contraction of aortic rings from different strains of rats: Sprague-Dawley (SD), Wistar, and Wistar Kyoto (WKY). Western blot analysis demonstrated that h1- and h2-calponins are present in aortic smooth muscle from adult SD rats but not Wistar or WKY rats. Nevertheless, h1-calponin is detectable in stomach from Wistar rats, although at a much lower level compared with that in the SD rat stomach. This suggests that a repressed expression of the gene, instead of a simple null mutation, may have caused its absence from the aortic smooth muscle. Despite the presence or absence of calponin, the aortic smooth muscles from the different strains of rats all develop contractions in response to the physiological agonist norepinephrine (NE) and following activation with the plasma membrane receptor-independent NaF induction. The data indicate that h1- and h2-calponins are not essential for NE- and NaF-induced contractions in aortic smooth muscle. The calponin-positive adult SD rat aorta was found to be more sensitive in contractile response to NE and NaF inductions compared with the calponin-negative rat aortae. This may imply a potential modulator function of calponin in the contraction of smooth muscle, whereas other contractile protein isoform differences between these rat strains may also play a role.This revised version was published online in September 2005 with corrections to the Cover Date. 相似文献
39.
P. Michael Stuart Rita K. Munn Edward DeMoll Jerold G. Woodward 《Human immunology》1995,43(4):269-275
We reported that antigenic preparations from Yersinia enterocolitica stimulate murine T cells in a manner consistent with that of superantigens. As a consequence we examined whether Y. enterocolitica antigenic preparations stimulate human T-cell cultures. Human T cells, enriched from peripheral blood lymphocytes, were stimulated to proliferate in the presence of Y. Enterocolitica cytoplasmic and membrane preparations. This activity has also been shown to be sensitive to protease treatment, indicating the presence of a protein, and when separated by ion-exchange chromatography a single peak of activity is resolved. Furthermore, this proliferation was inhibited, in a dose-dependent manner, by the presence of antibodies directed against MHC class II antigens, indicating a requirement for these molecules. When these cells were stained with a panel of Vβ-specific antibodies to determine if there was an enrichment of a particular Vβ-bearing T-cell subset after stimulation, results indicate a significant enrichment of T cells bearing Vβ3, Vβl2, Vβl4, and Vβl7 over controls. Taken together, these data are consistent with a Y. enterocolitica product acting as a superantigen for human T cells. 相似文献
40.
Integrating complementary and alternative medicine instruction into health professions education: organizational and instructional strategies. 总被引:1,自引:0,他引:1
Mary Y Lee Rita Benn Leslie Wimsatt Jane Cornman Joan Hedgecock Susan Gerik Janice Zeller Mary Jo Kreitzer Pamela Allweiss Claudia Finklestein Aviad Haramati 《Academic medicine》2007,82(10):939-945
A few years ago, the National Institutes of Health National Center for Complementary and Alternative Medicine funded a program called the Complementary and Alternative Medicine (CAM) Education Project. Grantees were 14 medical and nursing schools and the American Medical Student Association, which funded six additional medical schools. Grants were awarded in cohorts of five per year in 2000, 2001, and 2002-2003.The R25 grant recipients identified several major themes as crucial to the success of integrating CAM into health professions curricula. The rationale for integrating CAM curricula was in part to enable future health professionals to provide informed advice as patients dramatically increase the use of CAM. Success of new CAM education programs relied on leadership, including top-down support from institutions' highest administrators. Formal and informal engagement of key faculty and opinion leaders raised awareness, interest, and participation in programs. A range of faculty development efforts increased CAM-teaching capacity. The most effective strategies for integration addressed a key curriculum need and used some form of evidence-based practice framework. Most programs used a combination of instructional delivery strategies, including experiential components and online resources, to address the needs of learners while promoting a high level of ongoing interest in CAM topics. Institutions noted several benefits, including increased faculty development activities, the creation of new programs, and increased cross- and inter-university collaborations. Common challenges included the need for qualified faculty, crowded and changing curricula, a lack of defined best practices in CAM, and post-grant sustainability of programs. 相似文献