全文获取类型
收费全文 | 1372篇 |
免费 | 115篇 |
国内免费 | 12篇 |
学科分类
医药卫生 | 1499篇 |
出版年
2024年 | 1篇 |
2023年 | 13篇 |
2022年 | 8篇 |
2021年 | 45篇 |
2020年 | 29篇 |
2019年 | 39篇 |
2018年 | 43篇 |
2017年 | 37篇 |
2016年 | 49篇 |
2015年 | 66篇 |
2014年 | 65篇 |
2013年 | 87篇 |
2012年 | 132篇 |
2011年 | 140篇 |
2010年 | 77篇 |
2009年 | 43篇 |
2008年 | 90篇 |
2007年 | 111篇 |
2006年 | 97篇 |
2005年 | 75篇 |
2004年 | 84篇 |
2003年 | 56篇 |
2002年 | 54篇 |
2001年 | 6篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有1499条查询结果,搜索用时 562 毫秒
1.
Tselios Konstantinos Yap Kristy Su-Ying Pakchotanon Rattapol Polachek Ari Su Jiandong Urowitz Murray B. Gladman Dafna D. 《Clinical rheumatology》2019,38(1):269-269
Clinical Rheumatology - Prof. Ari Polachek on of the author of the published version of this article missed to add his second affiliation which is the Department of Rheumatology, Tel Aviv Sourasky... 相似文献
2.
3.
Thomas L. Patterson Shirley J. Semple Lydia R. Temoshok J. Hampton Atkinson J. Allen McCutchan Kristy A. Straits-Trster James L. Chandler Igor Grant 《Journal of Applied Biobehavioral Research》1993,1(1):64-87
The significance of life stress, coping, and social support was examined in relation to depressive symptomatology in a sample of 160 asymptomatic and mildly symptomatic HIV-antibody-positive (HIV+) men. The participants (mean age = 32 years) were interviewed about the life stress that they had experienced in the previous 6 相似文献
4.
Brenda M Sandmaier Storb Rainer Yanfang Liu Erlinda B Santos Eileen Bryant Friedrich G Schuening H Joachim Deeg Kristy Seidel Theodore Graham 《Transplant immunology》1996,4(4):271-274
920 cGy total body irradiation (TBI) is adequate for consistently successful engraftment of marrow from dog leukocyte antigen (DLA)-identical littermates; however, the dose is inadequate to ensure a marrow graft from DLA-nonidentical unrelated donors. Such mismatched grafts are successful only after 1800 cGy, given in three fractions. While anti-T-cell reagents enhance engraftment of DLA-identical littermate marrow after 920 cGy, they fail to be effective in the DLA-nonidentical setting. However, a monoclonal antibody (mAb) to CD44, S5, was found to be very effective in enhancing engraftment of DLA-nonidentical marrow. The current study asked whether mAb S5 was also effective in the setting of DLA-identical littermate transplants. To this purpose, the TBI dose was lowered to 450 cGy, a dose after which 70% of such grafts failed. Four dogs were treated with antibody S5, 0.2 mg/kg on days −7 though −2 (per previously published protocol), given 450 cGy TBI followed by marrow grafts from their DLA-identical littermates. All four dogs rejected their grafts; two of these died from marrow aplasia, and two survived with endogenous marrow recovery. This result was not statistically significantly different from that in 17, historical (n = 5) and concurrent (n = 12), control dogs where 11 of 17 animals rejected. Even if ten experimental animals were transplanted and all six remaining dogs engrafted, the results still would not have been significantly different from control. This result is in contrast to the successful engraftment promoted by pretreatment with antibody S5 of DLA-nonidentical unrelated dogs, consistent with the notion that different host cells are involved in graft rejection in the two disparate histocompatibility settings. 相似文献
5.
Tae Kim Kristy S Hendrich Kazuto Masamoto Seong-Gi Kim 《Journal of cerebral blood flow and metabolism》2007,27(6):1235-1247
Quantifying both arterial cerebral blood volume (CBV(a)) changes and total cerebral blood volume (CBV(t)) changes during neural activation can provide critical information about vascular control mechanisms, and help to identify the origins of neurovascular responses in conventional blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI). Cerebral blood flow (CBF), CBV(a), and CBV(t) were quantified by MRI at 9.4 T in isoflurane-anesthetized rats during 15-s duration forepaw stimulation. Cerebral blood flow and CBV(a) were simultaneously determined by modulation of tissue and vessel signals using arterial spin labeling, while CBV(t) was measured with a susceptibility-based contrast agent. Baseline versus stimulation values in a region centered over the somatosensory cortex were: CBF=150+/-18 versus 182+/-20 mL/100 g/min, CBV(a)=0.83+/-0.21 versus 1.17+/-0.30 mL/100 g, CBV(t)=3.10+/-0.55 versus 3.41+/-0.61 mL/100 g, and CBV(a)/CBV(t)=0.27+/-0.05 versus 0.34+/-0.06 (n=7, mean+/-s.d.). Neural activity-induced absolute changes in CBV(a) and CBV(t) are statistically equivalent and independent of the spatial extent of regional analysis. Under our conditions, increased CBV(t) during neural activation originates mainly from arterial rather than venous blood volume changes, and therefore a critical implication is that venous blood volume changes may be negligible in BOLD fMRI. 相似文献
6.
Osteoporosis is a chronic and potentially debilitating disease. A painful consequence of osteoporosis is a compression fracture of a vertebral body of the spine. These fractures can lead to physical deformities and emotional trauma. Treatment options for these fractures are limited and occasionally ineffective. New surgical advances in treating vertebro-compression fractures are evolving. Kyphoplasty is a new surgical procedure now being used to treat the painful compression fracture. 相似文献
7.
Scott L Kominsky Michele Doucet Kelly Brady Kristy L Weber 《Journal of bone and mineral research》2007,22(1):37-44
Bone metastases develop in approximately 30% of patients with RCC, and the mechanisms responsible for this phenomenon are unknown. We found that TGF-beta1 stimulation of RCC bone metastasis cells promotes tumor growth and bone destruction possibly by stimulating paracrine interactions between tumor cells and the bone. INTRODUCTION: Bone metastasis is a frequent complication and causes marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the specific mechanisms of RCC interaction with bone have been scarcely studied despite the inability to prevent or effectively treat bone metastasis. Bone is a reservoir for various growth factors including the pleiotropic cytokine TGF-beta1. TGF-beta1 has been shown to have tumor-supportive effects on advanced cancers and evidence suggests its involvement in promoting the development of breast cancer bone metastasis. Here, we studied the potential role of TGF-beta1 in the growth of RCC bone metastasis (RBM). MATERIALS AND METHODS: To inhibit TGF-beta1 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-betaRII cDNA were generated. The in vivo effect of TGF-beta1 on RBM tumor growth and osteolysis was determined by histological and radiographic analysis, respectively, of athymic nude mice after intratibial injection of parental, empty vector, or DN RBM cells. The in vitro effect of TGF-beta1 on RBM cell growth was determined after TGF-beta1 treatment by MTT assay. RESULTS: TGF-beta1 and the TGF-beta receptors I and II (TGF-betaRI/II) were consistently expressed in both RBM tissues and cell lines. Inhibition of TGF-beta1 signaling in RBM cells significantly reduced tumor establishment and osteolysis observed in vivo after injection into the murine tibia, although no effect on tumor establishment was observed after injection of RBM cells subcutaneously or into the renal subcapsule. Treatment of five RBM cell lines with TGF-beta1 in vitro either had no effect (2/5) or resulted in a significant inhibition (3/5) of cell growth, suggesting that TGF-beta1 may promote RBM tumor growth indirectly in vivo. CONCLUSIONS: TGF-beta1 stimulation of RBM cells plays a role in promoting tumor growth and subsequent osteolysis in vivo, likely through the initiation of tumor-promoting paracrine interactions between tumor cells and the bone microenvironment. These data suggest that inhibition of TGF-beta1 signaling may be useful in the treatment of RBM. 相似文献
8.
Stéphane Marinesco Kristy L. Duran William G. Wright† 《The Journal of physiology》2003,550(1):241-253
We investigated the neurobiological basis of variation in sensitization between three aplysiid species: Aplysia californica , Phyllaplysia taylori and Dolabrifera dolabrifera . We tested two different forms of sensitization induced by a noxious tail shock: local sensitization, expressed near the site of shock, and general sensitization, tested at remote sites. Aplysia showed both local and general sensitization, whereas Phyllaplysia demonstrated only local sensitization, and Dolabrifera lacked both forms of learning. We then investigated a neurobiological correlate of sensitization, heterosynaptic modulation of sensory neuron excitability by tail-nerve stimulation. We found (1) an increase in sensory neuron (SN) excitability after both ipsilateral and contralateral nerve stimulation in Aplysia , (2) a smaller and shorter-lasting increase in Phyllaplysia , and (3) no effect in Dolabrifera . Because sensitization in Aplysia is strongly correlated with serotonergic (5-HT) neuromodulation, we hypothesized that the observed interspecific variation in sensitization and SN neuromodulation might be correlated with variation in the anatomy and/or functional response of the serotonergic system. However, using immunohistochemistry, we found that all three species showed a similar pattern of 5-HT innervation. Furthermore, they also showed comparable 5-HT release evoked by tail-nerve shock, as measured with chronoamperometry. These observations indicate that interspecific variation in learning is correlated with differences in SN heterosynaptic plasticity within a backgound of evolutionary conservation in the 5-HT neuromodulatory pathway. We thus hypothesize that evolutionary changes in learning phenotype do not involve modifications of the 5-HT pathway per se , but rather, changes in the response of SNs to the activation of this or other neuromodulatory pathways upon noxious stimulation. 相似文献
9.
Kristy E Bailey Danny L Costantini Zhongli Cai Deborah A Scollard Zhuo Chen Raymond M Reilly Katherine A Vallis 《Journal of nuclear medicine》2007,48(9):1562-1570
(111)In-DTPA-human epidermal growth factor ((111)In-DTPA-hEGF [DTPA is diethylenetriaminepentaacetic acid]) is an Auger electron-emitting radiopharmaceutical that targets EGF receptor (EGFR)-positive cancer. The purpose of this study was to determine the effect of EGFR inhibition by gefitinib on the internalization, nuclear translocation, and cytotoxicity of (111)In-DTPA-hEGF in EGFR-overexpressing MDA-MB-468 human breast cancer cells. METHODS: Western blot analysis was used to determine the optimum concentration of gefitinib to abolish EGFR activation. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled hEGF were evaluated by confocal microscopy in MDA-MB-468 cells (1.3 x 10(6) EGFRs/cell) in the presence or absence of 1 microM gefitinib. The proportion of radioactivity partitioning into the cytoplasm and nucleus of MDA-MB-468 cells after incubation with (111)In-DTPA-hEGF for 24 h at 37 degrees C in the presence or absence of 1 microM gefitinib was measured by cell fractionation. DNA double-strand breaks caused by (111)In were quantified using the gamma-H2AX assay, and radiation-absorbed doses were estimated. Clonogenic survival assays were used to measure the cytotoxicity of (111)In-DTPA-hEGF alone or in combination with gefitinib. RESULTS: Gefitinib (1 microM) completely abolished EGFR phosphorylation in MDA-MB-468 cells. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled EGF were not diminished in gefitinib-treated cells compared with controls. The proportion of internalized (111)In that localized in the nucleus was statistically significantly greater when (111)In-DTPA-hEGF was combined with gefitinib compared with (111)In-DTPA-hEGF alone (mean +/- SD: 26.0% +/- 5.5% vs. 14.6% +/- 4.0%, respectively; P < 0.05). Induction of gamma-H2AX foci was greater in MDA-MB-468 cells that were treated with (111)In-DTPA-hEGF (250 ng/mL, 1.5 MBq/mL) plus gefitinib (1 microM ) compared with those treated with (111)In-DTPA-hEGF alone (mean +/- SD: 35 +/- 4 vs. 24 +/- 5 foci per nucleus, respectively). In clonogenic assays, a significant reduction in the surviving fraction was observed when (111)In-DTPA-hEGF (5 ng/mL, 6 MBq/microg) was combined with gefitinib (1 microM ) compared with (111)In-DTPA-hEGF alone (42.9% +/- 5.7% vs. 22.9% +/- 3.6%, respectively; P < 0.01). CONCLUSION: The efficacy of (111)In-DTPA-hEGF depends on internalization and nuclear uptake of the radionuclide. Nuclear uptake, DNA damage, and cytotoxicity are enhanced when (111)In-DTPA-hEGF is combined with gefitinib. These results suggest a potential therapeutic role for peptide receptor radionuclide therapy in combination with tyrosine kinase inhibitors. 相似文献
10.
Sharma R Yellowley CE Civelek M Ainslie K Hodgson L Tarbell JM Donahue HJ 《Annals of biomedical engineering》2002,30(3):371-378
Vascular smooth muscle cells (VSM) are normally exposed to transmural fluid flow shear stresses, and after vascular injury, blood flow shear stresses are imposed upon them. Since Ca2+ is a ubiquitous intracellular signaling molecule, we examined the effects of fluid flow on intracellular Ca2+ concentration in rat aortic smooth muscle cells to assess VSM responsiveness to shear stress. Cells loaded with fura 2 were exposed to steady flow shear stress levels of 0.5–10.0 dyn/cm2 in a parallel-plate flow chamber. The percentage of cells displaying a rise in cytosolic Ca2+ ion concentration ([Ca2+]i) increased in response to increasing flow, but there was no effect of flow on the ([Ca2+]i) amplitude of responding cells. Addition of Gd3+ (10 M) or thapsigargin (50 nM) significantly reduced the percentage of cells responding and the response amplitude, suggesting that influx of Ca2+ through ion channels and release from intracellular stores contribute to the rise in ([Ca2+]i) in response to flow. The addition of nifedipine (1 or 10 M) or ryanodine (10 M) also significantly reduced the response amplitude, further defining the role of ion channels and intracellular stores in the Ca2+ response. © 2002 Biomedical Engineering Society.
PAC2002: 8716Uv, 8719Uv, 8716Dg, 8719Ff 相似文献