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排序方式: 共有9089条查询结果,搜索用时 15 毫秒
71.
Laura M. Carlson Michelle Angrish Avanti V. Shirke Elizabeth G. Radke Brittany Schulz Andrew Kraft Richard Judson Grace Patlewicz Robyn Blain Cynthia Lin Nicole Vetter Courtney Lemeris Pamela Hartman Heidi Hubbard Xabier Arzuaga Allen Davis Laura V. Dishaw Ingrid L. Druwe Hillary Hollinger Ryan Jones J. Phillip Kaiser Lucina Lizarraga Pamela D. Noyes Michele Taylor Andrew J. Shapiro Antony J. Williams Kristina A. Thayer 《Environmental health perspectives》2022,130(5)
Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS.Objective: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing.Methods: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata.Results: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams.Discussion: Many of the PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343 相似文献
72.
Marijke Van Ghelue Hans L. Eriksen Vesna Ponjavic Toril Fagerheim Sten Andréasson Kristina Forsman-Semb 《Ophthalmic genetics》2013,34(4):197-209
Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disorder of photoreceptors. Mutations in several genes encoding different proteins of the visual cascade are described. The inheritance of two intragenic markers within the interstitial retinol binding protein (IRBP) gene was established in 45 Spanish families with a history of ARRP. Homozygosity mapping and cosegregation analyses were positive in 19 families. Only one heterozygous T-C transition at position 3024 (exon 1) was detected in one consanguineous family. This variant was identified as a rare polymorphism and was present in 5% of the chromosomes analyzed. 相似文献
73.
Holm K Larsson J Lövestam-Adrian M 《Documenta ophthalmologica. Advances in ophthalmology》2007,114(3):117-124
Purpose To study the relationship between foveal thickness assessed by optical coherence tomography (OCT) and foveal function measured
with multi focal electroretinography (mfERG) in patients with non-proliferative diabetic retinopathy, and with no previous
laser treatment.
Methods Twenty-six eyes from 18 diabetic patients (13 men), aged 59 years, (range 28–79 years), diabetes duration 15 years, (range
2–27 years), with a macular thickness between 200 and 600 μm were evaluated by mfERG, visual acuity (ETDRS score) and OCT. Mean amplitudes and implicit times of the mfERG responses were analyzed within the four innermost (14 degrees) of the six
concentric rings. For comparison with the results from the OCT (diameter of measured area = 6 mm) we analyzed the summed response
from the first and second ring (central zone), corresponding to the central area of the OCT. The third(zone 2) and fourth
(zone 3)of the four innermost of the six concentric rings measured by the mfERG corresponding to the second and third area
of OCT.
Results An increased macular thickness in the central area of the OCT correlated to reduced amplitudes (r = −0.541; P = 0.004) and prolonged implicit times (r = 0.548; P = 0.004) in the central zone of the mfERG, and inversely correlated with visual acuity, −0.49; P = 0.045.
Retinal thickness in the second area was correlated to prolonged implicit times in the second mfERG zone (r = −0.416; P = 0.034). No correlations were found for the third area of the OCT. When macular thickness exceeded 300 μm the decrease of
amplitudes and prolonged implicit times, measured by mfERG, seemed to be more pronounced.
Conclusion In conclusion increased macular thickness is correlated with reduced amplitudes and prolonged implicit times on the mf ERG
and worse visual acuity. 相似文献
74.
75.
76.
Gullbo J Lindhagen E Bashir-Hassan S Tullberg M Ehrsson H Lewensohn R Nygren P De La Torre M Luthman K Larsson R 《Investigational new drugs》2004,22(4):411-420
The novel alkylating dipeptide melphalanyl-p-L-fluorophenylalanine ethyl ester (J1) was evaluated for acute toxicity and antitumor activity in mice, with melphalan as a reference. To determine a safe and tolerable dose for efficacy studies the acute toxicity following intravenous injection in the tail vein was monitored using a 14-day schedule with up to four doses. The highest tested dose, 25 micromoles/kg, was considered close to this level, with minor effects on body weight gain but significant effects on hematological parameters. Melphalan and J1 appeared equitoxic with no statistically significant differences. Subsequently a mouse hollow fiber model was employed with subcutaneous implantation of fibers containing human tumor cells. Three different human tumor cell lines as well as two samples of primary human tumor cells (ovarian carcinoma and chronic lymphatic leukemia) were used as tumor models. At the dose level tested there was a marked and statistically significant decrease in both T-cell leukemia CCRF-CEM and small cell lung cancer NCI-H69 tumor cell growth and viability in response to J1 as compared with both placebo and melphalan treated groups. In primary ovarian carcinoma cells only J1 treatment resulted in significant tumor regression (net cell kill). In summary the results indicate that, despite an expected short half time in the blood circulation, the promising in vitro data from the previous studies of J1 seems translatable into the in vivo situation. At equal doses of alkylating units J1, compared to melphalan, was more active in the mouse hollow-fiber model, but showed similar general toxicity. 相似文献
77.
Maja Misirkic Kristina Janjetovic Ljubica Vucicevic Gordana Tovilovic Biljana Ristic Urosh Vilimanovich Ljubica Harhaji-Trajkovic Mirjana Sumarac-Dumanovic Dragan Micic Vladimir Bumbasirevic Vladimir Trajkovic 《Pharmacological research》2012,65(1):111-119
The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death. 相似文献
78.
Thrombopoietin Receptor Agonist Use in Children: Data From the Pediatric ITP Consortium of North America ICON2 Study 下载免费PDF全文
Cindy Neunert MD MSCS Jenny Despotovic DO MS Kristina Haley DO MCR Michele P. Lambert MD Kerri Nottage MD Kristin Shimano MD Carolyn Bennett MD Robert Klaassen MD FRCP Kimo Stine MD Alexis Thompson MD Yves Pastore MD Travis Brown BS Peter W. Forbes MA Rachael F. Grace MD MMSc 《Pediatric blood & cancer》2016,63(8):1407-1413
79.
Aseel Eid Isha Mhatre-Winters Ferass M. Sammoura Melissa K. Edler Richard von Stein Muhammad M. Hossain Yoonhee Han Miriam Lisci Kristina Carney Mary Konsolaki Ronald P. Hart Joan W. Bennett Jason R. Richardson 《Environmental health perspectives》2022,130(8)
Background: The interaction of aging-related, genetic, and environmental factors is thought to contribute to the etiology of late-onset, sporadic Alzheimer’s disease (AD). We previously reported that serum levels of p,p′-dichlorodiphenyldichloroethylene (DDE), a long-lasting metabolite of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT), were significantly elevated in patients with AD and associated with the risk of AD diagnosis. However, the mechanism by which DDT may contribute to AD pathogenesis is unknown.Objectives: This study sought to assess effects of DDT exposure on the amyloid pathway in multiple in vitro and in vivo models.Methods: Cultured cells (SH-SY5Y and primary neurons), transgenic flies overexpressing amyloid beta (), and C57BL/6J and 3xTG-AD mice were treated with DDT to assess impacts on the amyloid pathway. Real time quantitative polymerase chain reaction, multiplex assay, western immunoblotting and immunohistochemical methods were used to assess the effects of DDT on amyloid precursor protein (APP) and other contributors to amyloid processing and deposition.Results: Exposure to DDT revealed significantly higher APP mRNA and protein levels in immortalized and primary neurons, as well as in wild-type and AD-models. This was accompanied by higher levels of secreted in SH-SY5Y cells, an effect abolished by the sodium channel antagonist tetrodotoxin. Transgenic flies and 3xTG-AD mice had more pathology following DDT exposure. Furthermore, loss of the synaptic markers synaptophysin and PSD95 were observed in the cortex of the brains of 3xTG-AD mice.Discussion: Sporadic Alzheimer’s disease risk involves contributions from genetic and environmental factors. Here, we used multiple model systems, including primary neurons, transgenic flies, and mice to demonstrate the effects of DDT on APP and its pathological product . These data, combined with our previous epidemiological findings, provide a mechanistic framework by which DDT exposure may contribute to increased risk of AD by impacting the amyloid pathway. https://doi.org/10.1289/ EHP10576相似文献
80.