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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
13.
Oga Emmanuel. A. Peters Erica. N. Mark Katrina Trocin Kathleen Coleman-Cowger Victoria. H. 《Maternal and child health journal》2019,23(2):250-257
Maternal and Child Health Journal - Background Prenatal substance use screening is recommended. The 4 P’s Plus screener includes questions on perceived problematic substance use in parents... 相似文献
14.
Globally, the COVID‐19 pandemic has already led to major increases in unemployment and is expected to lead to unprecedented increases in poverty and food and nutrition insecurity, as well as poor health outcomes. Families where young children, youth, pregnant and lactating women live need to be protected against the ongoing protracted pandemic and the aftershocks that are very likely to follow for years to come. The future wellbeing of the vast majority of the world now depends on reconfiguring the current ineffective food, nutrition, health, and social protection systems to ensure food and nutrition security for all. Because food, nutrition, health, and socio‐economic outcomes are intimately inter‐linked, it is essential that we find out how to effectively address the need to reconfigure and to provide better intersecoral coordination among global and local food, health care, and social protection systems taking equity and sutainability principles into account. Implementation science research informed by complex adaptive sytems frameworks will be needed to fill in the major knowledge gaps. Not doing so will not only put the development of individuals at further risk, but also negatively impact on the development potential of entire nations and ultimately our planet. 相似文献
15.
James R. Barrett MD Victoria Rendell MD Courtney Pokrzywa MD Alexandra G. Lopez-Aguiar MD John Cannon BA George A. Poultsides MD MS Flavio Rocha MD Angelena Crown MD Eliza Beal MD Timothy Michael Pawlik MD MPH PhD Ryan Fields MD Roheena Z. Panni MD MPHS Paula Smith MD Kamran Idrees MD Clifford Cho MD Megan Beems MD Shishir Maithel MD Sharon Weber MD Daniel Erik Abbott MD 《Journal of surgical oncology》2020,121(7):1067-1073
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Victoria Alegría‐Landa Heinz Kutzner Luis Requena 《Journal of cutaneous pathology》2019,46(11):867-871
Carcinosarcomas are biphasic tumors composed of admixed malignant epithelial and mesenchymal components. Numerous terms have been used to name such neoplasms; therefore, terminological confusion is frequent. Most examples of carcinosarcomas are encountered in non‐cutaneous sites, with approximately 100 cases of cutaneous carcinosarcomas reported so far in the English literature. Although different theories have been suggested to explain the occurrence of these peculiar neoplasms, histogenetic mechanisms should be better hypothesized depending on each individual case. Even though prognosis tends to be related to the specific components of the lesion, especially the epithelial one, it seems that cases of cutaneous localization usually have a better outcome. We report an exceedingly rare case of syringocystadenocarcinoma papilliferum which showed an atypical stroma with sarcomatoid appearance, and highlight that the terminology used for this spectrum of lesions is disorganized and confusing. 相似文献
18.
John P. Sundberg Kathleen A. Silva Victoria E. Kennedy John J. Wilson Nicholas E. Gott Beth A. Sundberg Derry C. Roopenian 《Experimental dermatology》2019,28(9):1091-1093
2‐deoxy D‐glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T‐cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell‐mediated autoimmune mouse disease, alopecia areata. 相似文献
19.
Peter D. Baade David C. Whiteman Monika Janda Anne E. Cust Rachel E. Neale Bernard Mark Smithers Adele C. Green Kiarash Khosrotehrani Victoria Mar H. Peter Soyer Joanne F. Aitken 《International journal of cancer. Journal international du cancer》2020,147(5):1391-1396
There is little long-term follow-up information about how the number of melanoma deaths and case fatality vary over time according to the measured thickness of melanoma at diagnosis. This population-based longitudinal cohort study examines patterns and trends in case fatality among 44,531 people in Queensland (Australia) diagnosed with a single invasive melanoma (International Classification of Diseases for Oncology, third revision [ICD-O-3], C44, Morphology 872–879) between 1987 and 2011, including 11,883 diagnosed between 1987 and 1996, with up to 20 years follow-up (to December 2016). The 20-year case fatality increased by thickness, with the percentage of melanoma deaths within 20 years of diagnosis being up to 4.8% for melanomas with measured thickness <0.80 mm, 10.6% for tumors 0.8 to <1.0 mm and generally more than 30% for melanomas measuring 3 mm and more. For melanomas <1.0 mm, most deaths occurred between 5 and 20 years after diagnosis, whereas for thicker melanomas the reverse was true with most deaths occurring within the first 5 years. Five-year case fatality decreased over successive calendar time periods for melanomas <1.0 mm, but not for melanomas ≥1.0 mm. These findings demonstrate that the time course for fatal melanomas varies markedly according to tumor thickness at diagnosis. Improved understanding of the patient factors and characteristics of melanomas, in addition to tumor thickness, which increase the likelihood of progression, is needed to guide clinical diagnosis, communication with patients and ongoing surveillance pathways of patients with potentially fatal lesions. 相似文献