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191.
Anna Cseke Theresa Schwarz Sankalp Jain Simon Decker Kerstin Vogl Ernst Urban Gerhard F. Ecker 《Archiv der Pharmazie》2020,353(3):1900269
P-glycoprotein (P-gp) is an ATP-dependent efflux pump that has a marked impact on the absorption, distribution, and excretion of therapeutic drugs. As P-gp inhibition can result in drug–drug interactions and altered drug bioavailability, identifying molecular properties that are linked to inhibition is of great interest in drug development. In this study, we combined chemical synthesis, in vitro testing, quantitative structure–activity relationship analysis, and docking studies to investigate the role of hydrogen bond (H-bond) donor/acceptor properties in transporter–ligand interaction. In a previous work, it has been shown that propafenone analogs with a 4-hydroxy-4-piperidine moiety exhibit a generally 10-fold higher P-gp inhibitory activity than expected based on their lipophilicity. Here, we specifically expanded the data set by introducing substituents at position 4 of the 4-phenylpiperidine moiety to assess the importance of H-bond donor/acceptor features in this region. The results suggest that indeed an H-bond acceptor, such as hydroxy and methoxy, increases the affinity by forming a H-bond with Tyr310. 相似文献
192.
Tyler Sandow John Pavlus David Field Eduardo Lacayo Emil Cohen George Lynskey Theresa Caridi Donna Buckley John Cardella Bhaskar Kallakury James Spies Alexander Y. Kim 《Journal of vascular and interventional radiology : JVIR》2019,30(7):995-1003
PurposeTo evaluate tumor response to transarterial chemoembolization as well as biologic characteristics of the tumor as predictors of recurrence after transplantation in patients with hepatocellular carcinoma (HCC) who were bridged or down-staged to liver transplantation.Materials and MethodsAn institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, single-institution retrospective analysis was performed on all patients with HCC who were treated with the use of conventional transarterial chemoembolization or transarterial chemoembolization with drug-eluting embolics (DEE) over a 12-year period and who subsequently underwent liver transplantation (n = 142). Treatment response was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) imaging criteria and then correlated with tumor characteristics and recurrence. Of the 142 patients followed after transplantation, 127 had imaging after transarterial chemoembolization but before transplantation. Imaging response and post-transplantation recurrence were correlated with patient demographics, liver function, and tumor morphology. HCC recurred in 9 patients (mean time from transplantation, 526 days). Recurrence was analyzed with the use of univariate and multivariate statistics. Kaplan-Meier recurrence-free survival curves were calculated based on immediate imaging response before transplantation with the use of the log-rank test.ResultsBefore transplantation, 57% of patients (72/127) demonstrated complete response (CR) and 24% (31/127) showed partial response (PR). Complete pathologic necrosis occurred in 54% (39/72) of CR patients and 20% (6/31) of PR patients. Poor treatment response, defined as stable disease (SD) or progressive disease (PD), occurred in 18% of patients (24/127) before transplantation and was present in 67% of cases of recurrence (6/9; P < .001). Post-transplantation recurrence was present in 1.4% of patients (1/71) with CR and in 6.5% of patients (2/31) with PR. In patients with SD after transarterial chemoembolization, HCC recurred in 18.8% of transplant patients (3/16) and in 43% of patients (3/7) with PD. Larger pretreatment tumor size (P = .05), higher Child-Pugh score (P = .002), higher tumor grade at explantation (P = .04), and lymphovascular invasion at explantation (P = .008) also were associated with increased incidence of post-transplantation recurrence.ConclusionsPoor tumor response to transarterial chemoembolization before transplantation identifies patients at increased risk for post-transplantation recurrence. 相似文献
193.
Merchant Rutvij Goldin Aleah Manjanatha Deepa Harter Claire Chandler Judy Lipp Amanda Nguyen Theresa Naslund John A. 《The Psychiatric quarterly》2022,93(2):613-625
Psychiatric Quarterly - This study investigated whether with disruptions in care due to the COVID-19 pandemic, persons who self-identified as living with a mental health condition increased their... 相似文献
194.
Gabbert Carolin König Inke R. Lüth Theresa Kolms Beke Kasten Meike Vollstedt Eva-Juliane Balck Alexander Grünewald Anne Klein Christine Trinh Joanne 《Journal of neurology》2022,269(8):4195-4203
Journal of Neurology - Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene–environment interactions have been found... 相似文献
195.
Long‐Term Trajectories of PTSD in Vietnam‐Era Veterans: The Course and Consequences of PTSD in Twins 下载免费PDF全文
Kathryn M. Magruder Jack Goldberg Christopher W. Forsberg Matthew J. Friedman Brett T. Litz Viola Vaccarino Patrick J. Heagerty Theresa C. Gleason Grant D. Huang Nicholas L. Smith 《Journal of traumatic stress》2016,29(1):5-16
We estimated the temporal course of posttraumatic stress disorder (PTSD) in Vietnam‐era veterans using a national sample of male twins with a 20‐year follow‐up. The complete sample included those twins with a PTSD diagnostic assessment in 1992 and who completed a DSM‐IV PTSD diagnostic assessment and a self‐report PTSD checklist in 2012 (n = 4,138). Using PTSD diagnostic data, we classified veterans into 5 mutually exclusive groups, including those who never had PTSD, and 4 PTSD trajectory groups: (a) early recovery, (b) late recovery, (c) late onset, and (d) chronic. The majority of veterans remained unaffected by PTSD throughout their lives (79.05% of those with theater service, 90.85% of those with nontheater service); however, an important minority (10.50% of theater veterans, 4.45% of nontheater veterans) in 2012 had current PTSD that was either late onset (6.55% theater, 3.29% nontheater) or chronic (3.95% theater, 1.16% nontheater). The distribution of trajectories was significantly different by theater service (p < .001). PTSD remains a prominent issue for many Vietnam‐era veterans, especially for those who served in Vietnam. 相似文献
196.
Chantal Loirat Fadi Fakhouri Gema Ariceta Nesrin Besbas Martin Bitzan Anna Bjerre Rosanna Coppo Francesco Emma Sally Johnson Diana Karpman Daniel Landau Craig B Langman Anne-Laure Lapeyraque Christoph Licht Carla Nester Carmine Pecoraro Magdalena Riedl Nicole C. A. J. van de Kar Johan Van de Walle Marina Vivarelli Véronique Frémeaux-Bacchi for HUS International 《Pediatric nephrology (Berlin, Germany)》2016,31(1):15-39
197.
Insight from Frogs: Sonic Hedgehog Gene Expression and a Re‐evaluation of the Vertebrate Odontogenic Band 下载免费PDF全文
While the identification of conserved processes across multiple taxa leads to an understanding of fundamental developmental mechanisms, the ways in which different animals fail to conform to common developmental processes can elucidate how evolution modifies development to result in the vast array of morphologies seen today—the developmental mechanisms that lead to anatomical variation. Odontogenesis—how teeth are initiated and formed—is well suited to the examination of both developmental conservation and phenotypic diversity. We suggest here that the study of early tooth development, the period of odontogenic band development, reveals departures from conserved mechanisms that question the role of players in the developmental process. In the earliest stages of odontogenesis, Sonic hedgehog (Shh) gene expression is interpreted as critical evidence of tooth initiation prior to any histological indication. However, a detailed examination of studies of tooth development across a wide range of taxa reveals that several vertebrate species fail to conform to the expectations of the Shh Consensus Model, calling for a reconsideration of the assumed causality of epithelial Shh in tooth initiation. We present new Shh gene expression data for an amphibian, the frog Silurana (Xenopus) tropicalis. In these animals, craniofacial and odontogenic developmental processes are more disjunct, and thereby provide a natural test of the hypothesis that Shh is immediately required for subsequent tooth development. Our results suggest that Shh expression may actually be related to the formation of the mouth rather than a required precursor to subsequent tooth formation. Anat Rec, 299:1099–1109, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
198.
Theresa Dever Fitzgerald Jaime Williams Lisa Lix Sharmeen Zahir Dennis Alfano 《Disability and rehabilitation》2016,38(11):1041-1052
Purpose: The purpose of this study was to determine whether providing fall risk information to long-term care (LTC) nurses affects restraint use, activities of daily living (ADL), falls, and nurse fears about patient falls. Methods: One-hundred and fifty LTC residents were randomized to a fall risk assessment intervention or care-as-usual group. Hypotheses were tested using analyses of variance and path analyses. Results: Restraint use was associated with lower ADL scores. In the intervention group, there ceased to be significant relationships between nurse fears about falls and patient falls (after controlling for actual patient risk; post-intervention, nurse fears about falls were based on realistic appraisals), and between fears and restraints (i.e. unjustified nurse fears became less likely to lead to unjustified restraint use). No group differences in falls were identified. Conclusion: Despite a lack of group differences in falls, results show initial promise in potentially impacting resident care. Increasing intervention intensity may lead to fall reductions in future research.
- Implications for Rehabilitation
Given the high prevalence rates of falls in LTC and associated injuries, prevention programs are important.
Nurse fears about patient falls may impact upon restraint use which, when excessive, can interfere with the patient’s ability to perform ADL. Excessive restraint use, due to unjustified nurse fears, could also lead to falls.
Providing accurate, concise information to nursing staff about patient fall risk may aid in reducing the association between unjustified nurse fears and the resulting restraint use that can have potential negative consequences.
199.
Joanne J Sohn Theresa M Gruber Joanne L Zahorsky-Reeves Greg W Lawson 《Journal of the American Association for Laboratory Animal Science》2016,55(2):199-203
Short-chain cyanoacrylates (SCCA), such as ethyl-2-cyanoacrylate (KrazyGlue, Aron Alpha, Columbus, OH) are commonly used as commercial fast-acting glues. Although once used in clinical medicine as skin adhesives, these products caused tissue toxicity and thus their use in live tissue was discontinued. SCCA were replaced by longer-chain versions (LCCA), such as butyl-cyanoacrylate (Vetbond, 3M, St Paul, Minnesota), which were found to be less toxic than the short-chain formulations. Some researchers prefer to use SCCA due to the belief that they create a stronger bond than do the longer-chain counterparts. In survival surgeries, we compared the bone thickness, bone necrosis, fibrosis, inflammation, and bone regeneration in the calvaria of control (naïve), surgery-only, SCCA-treated, and LCCA-treated mice (n = 20 per group). At 1 and 14 d after surgery, all mice except those treated with SCCA showed statistically similar bone measurements to those of the naive control group. The SCCA group had significantly less bone regeneration than did all other groups. These results suggest that the application of SCCA causes bone damage resulting in the loss of bone regeneration. This finding may assist investigators in choosing a tissue glue for their studies and may support the IACUC in advocating the use of pharmaceutical-grade tissue glues.Abbreviations: LCCA, long-chain cyanoacrylates; SCCA, short-chain cyanoacrylatesCyanoacrylates have been used as tissue adhesives since their synthesis in 1949.6 Synthetic cyanoacrylate adhesives belong in the family of liquid monomers formed by alkyl esters of 2-cyanoacrylic acid. The basic formula of the cyanoacrylate adhesive (alkyl-2-cyanoacrylate) has been manipulated to form different cyanoacrylate adhesives with different properties.29 Several 2-cyanoacrylate esters have been synthesized by changing the length of the alkyl chain attached.42 The first cyanoacrylates were short-chained, poorly manufactured, and toxic to animals at pharmacologic doses.24 Short-chain cyanoacrylates (SCCA), such as methyl-2-cyanoacrylate and ethyl-2-cyanoacrylate (KrazyGlue [Aron Alpha, Columbus, OH]), continue to be used as fast-acting adhesives.5 Although appropriated as tissue glues soon after their discovery, these early SCCA caused tissue toxicity and thus were discontinued in the clinical arena.4 Research showed that changing the type of alcohol in the compound to one with a longer molecular chain reduced tissue toxicity. Over time, nontoxic, longer-chain cyanoacrylates (LCCA), such as butyl-cyanoacrylate (Vetbond [3M, St Paul, Minnesota]) and octylcyanoacrylate, were manufactured, leading to their use once again in clinical medicine33 (Figure 1).Open in a separate windowFigure 1.Trade names for different types of cyanoacrylates.Many researchers contend that SCCA is superior to LCCA in regard to the strength and tenacity of the bond when used to create cranial windows and as an application prior to an overlay of acrylic for cranial implants. However, SCCA is not pharmaceutical-grade, as mandated by the USDA in Policy 32 and the Guide for the Care and Use of Laboratory Animals,22 and therefore can only be used after specific review and approval by an institution''s IACUC. The determination for substitution is generally based on scientific necessity or compound availability.In this study, the effects of applying an SCCA product to mice calvaria were compared with those of an LCCA glue. Specifically, we evaluated bone regeneration, osteocyte numbers, inflammation, and bone remodeling at 2 time points after application. We hypothesized that mice calvaria treated with the SCCA product would show signs of toxicity, compared with skulls treated with the LCCA glue. 相似文献
200.