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Sung‐Hyun Hwang Myung‐Chul Kim Sumin Ji Yeseul Yang Yeji Jeong Yongbaek Kim 《Cancer science》2019,110(4):1256-1267
Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy. 相似文献
3.
Kun‐Yong Sung Seungkoo Lee Yeonjin Jeong Sang‐Yeul Lee 《The Australasian journal of dermatology》2021,62(1):60-63
A classic pilomatricoma, which usually presents with an asymptomatic, solitary, firm, subcutaneous nodule in the head, neck, or extremities of the paediatric population, is easily diagnosed based on its characteristic clinical and histopathological features. However, its variants often pose particular diagnostic challenges to clinicians due to their rarity and diverse clinicopathological features. We present a new pseudocystic variant, manifesting as solid lesions floating in a fluid‐filled sac. 相似文献
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Paul Tetteh Asare Nadeeka Bandara Tae-Yong Jeong Sangryeol Ryu Jochen Klumpp Kwang-Pyo Kim 《Archives of virology》2015,160(10):2647-2650
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M.‐Q. Man L. Ye L. Hu S. Jeong P. M. Elias C. Lv 《Clinical and experimental dermatology》2019,44(6):654-657
While therapeutic approaches for psoriasis are widely available, preventive regimens are lacking. We aimed to determine whether improvements in epidermal function could prevent psoriasis relapse. Two self‐controlled cohort studies were designed, enrolling two cohorts of patients with psoriasis (n = 30 and n = 60) to be treated topically with an in‐house‐prepared emollient or ATOPALM® cream applied twice daily to one forearm for 20 and 30 days, respectively, while the same sites on the contralateral arm served as the untreated control. Epidermal function on both arms was assessed prior to and at the end of the trials. Delayed relapse on the treated arm was seen in 54.5% and 71% of patients in the first and second cohort, respectively. The time of psoriatic relapse correlated with the extent of abnormalities in baseline epidermal function. These results suggest that improvements in epidermal function with topical emollients can prevent/attenuate the development of psoriasis. 相似文献
7.
Comparative outcomes of vascular access in patients older than 70 years with end-stage renal disease
Deokbi Hwang Sujin Park Hyung-Kee Kim Seung Huh 《Journal of vascular surgery》2019,69(4):1196-1206.e5
Objective
The advantage of arteriovenous fistulas (AVFs) in older patients requiring dialysis is controversial. We reviewed our vascular access experience in patients ≥70 years of age (older group) compared with younger patients.Methods
We analyzed consecutive patients who underwent access surgery between 2013 and 2016. Primary success (PS) and primary patency (PP) data were analyzed between the older and younger groups before and after propensity score matching of the patients' characteristics and access composition. PS was defined as the achievement of access function that was amenable to two sessions of successful cannulation without early occlusion or maturation failure requiring revision. PP was defined as the time with uninterrupted patency without intervention.Results
A total of 594 consecutive accesses were created among 563 patients, of whom 119 were allocated into each group after propensity score matching. In the whole cohort, 193 accesses (32.5%) were performed in older patients. AVFs were performed in 130 (67.4%) older patients and 293 (73.1%) younger patients. Regarding AVFs, the PS rate (83.6% in the older group vs 94.3% in the younger group; P = .001) and the overall PP at 6 and 12 months (73.1% and 57.1%, respectively, in the older group vs 86.7% and 77.7%, respectively, in the younger group; P = .009) were lower in the older group than in the younger group. However, no differences were found in the PS and PP rates for arteriovenous grafts between groups. Regarding the AVF location, the PS rate for forearm AVFs was significantly lower in the older group than in the younger group (76% vs 93%; P < .001); however, the PS rate of the upper arm was not different between the groups (94% vs 97%; P = .425). In the patients with PS, the PP rate of AVFs was similar between the two groups. In the older group with forearm AVFs, the median diameter of the radial artery was larger in the patients with PS than in the patients without PS (2.20 mm with PS vs 2.00 mm without PS; P = .008). The propensity score matching results demonstrated similar trends for the whole cohort, with lower PS (P = .042) and PP rates (P = .023) for AVF in the older group.Conclusions
The outcomes after AVF were poorer in the older group than in the younger group, which was primarily due to unsatisfactory outcomes in patients with forearm AVFs. Thus, stricter criteria, especially regarding the radial artery diameter, should be applied for forearm AVFs in older patients, and additional research is necessary to delineate the risk factors for primary failure. 相似文献8.
William B. Parker Paula W. Allan William R. Waud Jeong Hong Melissa Gilbert-Ross B. R. Achyut Disha Joshi Turang Behbahani Regina Rab Steven E. Ealick Eric J. Sorscher 《Cancer chemotherapy and pharmacology》2020,85(3):573-583
Treatment with fludarabine phosphate (9-β-D-arabinofuranosyl-2-F-adenine 5′-phosphate, F-araAMP) leads to regressions and cures of human tumor xenografts that express Escherichia coli purine nucleoside phosphorylase (EcPNP). This occurs despite the fact that fludarabine (F-araA) is a relatively poor substrate for EcPNP, and is cleaved to liberate 2-fluoroadenine at a rate only 0.3% that of the natural E. coli PNP substrate, adenosine. In this study, we investigated a panel of naturally occurring PNPs to identify more efficient enzymes that may be suitable for metabolizing F-araA as part of experimental cancer therapy. We show that Trichomonas vaginalis PNP (TvPNP) cleaves F-araA with a catalytic efficiency 25-fold greater than the prototypic E. coli enzyme. Cellular extracts from human glioma cells (D54) transduced with lentivirus stably expressing TvPNP (D54/TvPNP) were found to cleave F-araA at a rate similar to extracts from D54 cells expressing EcPNP, although much less enzyme was expressed per cell in the TvPNP transduced condition. As a test of safety and efficacy using TvPNP, human head and neck squamous cell carcinoma (FaDu) xenografts expressing TvPNP were studied in nude mice and shown to exhibit robust tumor regressions, albeit with partial weight loss that resolved post-therapy. F-araAMP was also a very effective treatment for mice bearing D54/TvPNP xenografts in which approximately 10% of tumor cells expressed the enzyme, indicating pronounced ability to kill non-transduced tumor cells (high bystander activity). Moreover, F-araAMP demonstrated activity against D54 tumors injected with an E1, E3 deleted adenoviral vector encoding TvPNP. In that setting, despite higher F-araA cleavage activity using TvPNP, tumor responses were similar to those obtained with EcPNP, indicating factors other than F-Ade production may limit regressions of the D54 murine xenograft model. Our results establish that TvPNP is a favorable enzyme for activating F-araA, and support further studies in combination with F-araAMP for difficult-to-treat human cancers. 相似文献
9.
Catherine L. Omosule Dominique Joseph Brooke Weiler Victoria L. Gremminger Spencer Silvey Youngjae Jeong Ashique Rafique Pamela Krueger Sandra Kleiner Charlotte L. Phillips 《Journal of bone and mineral research》2022,37(5):938-953
Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-β (TGF-β) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+/G610C) mice using specific monoclonal antibodies. Male and female Wt and +/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16 weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro–computed tomography (μCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +/G610C musculoskeleton, and was detrimental to bone strength in male +/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +/G610C mice, but had minimal skeletal impact in +/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +/G610C mice. © 2022 American Society for Bone and Mineral Research (ASBMR). 相似文献
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