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1.
Fiore Manganelli Silvia Parisi Maria Nolano Francesco Miceli Stefano Tozza Chiara Pisciotta Rosa Iodice Vincenzo Provitera Rita Cicatiello Stephan Zuchner Maurizio Taglialatela Tommaso Russo Lucio Santoro 《Journal of the peripheral nervous system : JPNS》2019,24(4):330-339
The development of patient‐specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot‐Marie‐Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post‐mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post‐mitotic neurons within 6‐8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post‐mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient‐derived iPSCs into post‐mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1‐CMT disease. 相似文献
2.
Merashli Mira Bucci Tommaso Pastori Daniele Pignatelli Pasquale Ames Paul R. J. 《Clinical rheumatology》2022,41(12):3769-3776
Clinical Rheumatology - To perform a systematic review and meta-analysis of studies reporting data on atherosclerosis and inflammatory markers in familial Mediterranean fever (FMF). EMBASE and... 相似文献
3.
4.
Alessandro De Cassai Tommaso Tonetti Helmut Galligioni Carlo Ori 《Brazilian Journal of Anesthesiology》2019,69(1):95-98
Background and objective
Erector spinae plane block is a valid technique to provide simultaneously analgesia for combined thoracic and abdominal surgery.Case report
A patient underwent open esophagectomy followed by reconstructive esophagogastroplasty but refused thoracic epidural analgesia; a multi‐modal analgesia with a multiple erector spinae plane block was then planned. Three erector spinae plane catheters (T5 and T10 on the right side and T9 on the left side) for continuous analgesia were placed before surgery. During the first 48 h pain was never reported in the thoracic area but the patient reported multiple times to feel a pain well localized in epigastrium, but never localized in any other abdominal quadrant.Discussion
Erector spinae plane block is a valid technique to provide analgesia simultaneously for combined thoracic and abdominal surgery and could be a valid alternative strategy if the use of epidural analgesia is contraindicated. 相似文献5.
Filippo Pietrantonio Christian Cotsoglou Giovanni Fucà Salvatore Lo Vullo Federico Nichetti Massimo Milione Jorgelina Coppa Marta Vaiani Alessandra Alessi Michele Prisciandaro Michele Droz-Dit Busset Federica Morano Salvatore Corallo Silvia Lazzati Maria Antista Alessia Mennitto Giovanni Randon Alessandra Raimondi Vincenzo Mazzaferro 《Clinical colorectal cancer》2019,18(1):34-43.e6
Background
In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.Patients and Methods
This was a single-center phase II study enrolling patients with liver-limited, borderline resectable disease and/or high-risk features. Patients received 5 preoperative and 4 postoperative cycles of biweekly COI-B (irinotecan 180 mg/m2 and bevacizumab 5 mg/Kg on day 1, oxaliplatin 85 mg/m2 on day 2, and capecitabine 1000 mg/m2 twice a day on days 2 to 6). The primary endpoint was pathologic response rate in the intention-to-treat population. A Simon 2-stage design was adopted to detect an increase from 30% to 50% with a power of 90%. Dynamic imaging biomarkers (early tumor shrinkage [ETS], deepness of response, maximum standardized uptake volume [SUVmax]/regression index) and next generation sequencing data were explored as surrogates.Results
From June 2013 to March 2017, 46 patients were enrolled. Pathologic response was achieved in 63% patients (endpoint met), and responders achieved significantly better survival outcomes with respect to non-responders. The most frequent grade 3/4 adverse events were diarrhea and neutropenia (8.7%) in the preoperative phase and thromboembolic events (5.9%) in the postoperative phase. ETS and lower SUV-2 were significantly associated with pathologic response.Conclusion
The COI-B regimen is a feasible and highly active perioperative strategy in patients with molecularly unselected, potentially resectable CRCLM. ETS and SUV-2 have a promising role as imaging-based biomarkers for pathologic response. 相似文献6.
Annalisa Guida Gwnaël Le Teuff Carolina Alves Emeline Colomba Vincenzo Di Nunno Lisa Derosa Ronan Flippot Bernard Escudier Laurence Albiges 《Oncotarget》2020,11(49):4582
Majority of patients with clear-cell renal cell carcinoma (ccRCC) at first line (1L) treatment are classified in the intermediate-risk (IR) subgroup according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score. As these patients have different prognosis, the aim of this study is to better characterize IR patients in order to better tailor the treatment. Retrospective analysis was performed from IGReCC (Institut Gustave Roussy Renal Cell Carcinoma) database. Overall survival (OS) was defined from start of 1L therapy to death or last follow-up. A multivariable Cox model with backward selection procedure (α = 0.01) and a Classification and Regression Tree (CART) analysis were performed to identify which prognostic factors were associated to OS in IR patients.From 2005 to 2017, 777 patients with ccRCC were treated with an anti-VEGF 1L therapy. Among 571 evaluable patients for IMDC score, 290 (51%) were classified as IR. With median follow-up 5.8 years (min: 0, max: 12.4) 212 deaths (73%) were observed and median OS was 25 months. Only platelet count was significantly associated to OS (hazard ratio 1.88 [95% CI 1.27–2.88] p = 0.0017). Median OS for patients with PLT > UNL was 18 months [95% CI 12–23] versus 29 months [95% CI 21.4–35.7] for patients with normal PLT count. The selection of PLT count was confirmed on bootstrap samples and was also selected for the first split of the CART-tree analysis.Patients in the IR group have a heterogeneous prognosis. Elevated PLT count seems identifies a subgroup of patients with poor outcome in the IMDC intermediate-risk population with ccRCC. 相似文献
7.
Simona Coco Simona Boccardo Marco Mora Vincenzo Fontana Irene Vanni Carlo Genova Angela Alama Sandra Salvi Maria Giovanna Dal Bello Silvia Bonfiglio Erika Rijavec Claudio Sini Giulia Barletta Federica Biello Franca Carli Zita Cavalieri Giovanni Burrafato Luca Longo Francesco Grossi 《Clinical breast cancer》2021,21(3):218-230.e6
IntroductionBreast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk.Patients and MethodsThirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups.ResultsEstrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform β was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer.ConclusionThe decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation. 相似文献
8.
Angius Gesuino Tomao Silverio Stati Valeria Vici Patrizia Bianco Vincenzo Tomao Federica 《Cancer chemotherapy and pharmacology》2020,85(1):9-20
Cancer Chemotherapy and Pharmacology - Checkpoint kinases 1 and 2 (CHK1 and CHK2) are important multifunctional proteins of the kinase family. Their main function is to regulate DNA replication and... 相似文献
9.
Federica Miglietta Maria Vittoria Dieci Vassilena Tsvetkova Gaia Griguolo Grazia Vernaci Alice Menichetti Giovanni Faggioni Tommaso Giarratano Eleonora Mioranza Elisa Genovesi Enrico Cumerlato Michele Bottosso Tania Saibene Silvia Michieletto Marcello Lo Mele Pierfranco Conte Valentina Guarneri 《The oncologist》2020,25(9):e1355-e1362
10.
Sara Caratelli Roberto Arriga Tommaso Sconocchia Alessio Ottaviani Giulia Lanzilli Donatella Pastore Carlo Cenciarelli Adriano Venditti Maria Ilaria Del Principe Davide Lauro Elisa Landoni Hongwei Du Barbara Savoldo Soldano Ferrone Gianpietro Dotti Giuseppe Sconocchia 《International journal of cancer. Journal international du cancer》2020,146(1):236-247
Cetuximab and panitumumab bind the human epidermal growth factor receptor (EGFR). Although the chimeric cetuximab (IgG1) triggers antibody-dependent-cellular-cytotoxicity (ADCC) of EGFR positive target cells, panitumumab (a human IgG2) does not. The inability of panitumumab to trigger ADCC reflects the poor binding affinity of human IgG2 Fc for the FcγRIII (CD16) on natural killer (NK) cells. However, both human IgG1 and IgG2 bind the FcγRII (CD32A) to a similar extent. Our study compares the ability of T cells, engineered with a novel low-affinity CD32A131R-chimeric receptor (CR), and those engineered with the low-affinity CD16158F-CR T cells, in eliminating EGFR positive epithelial cancer cells (ECCs) in combination with cetuximab or panitumumab. After T-cell transduction, the percentage of CD32A131R-CR T cells was 74 ± 10%, whereas the percentage of CD16158F-CR T cells was 46 ± 15%. Only CD32A131R-CR T cells bound panitumumab. CD32A131R-CR T cells combined with the mAb 8.26 (anti-CD32) and CD16158F-CR T cells combined with the mAb 3g8 (anti-CD16) eliminated colorectal carcinoma (CRC), HCT116FcγR+ cells, in a reverse ADCC assay in vitro. Crosslinking of CD32A131R-CR on T cells by cetuximab or panitumumab and CD16158F-CR T cells by cetuximab induced elimination of triple negative breast cancer (TNBC) MDA-MB-468 cells, and the secretion of interferon gamma and tumor necrosis factor alpha. Neither cetuximab nor panitumumab induced Fcγ-CR T antitumor activity against Kirsten rat sarcoma (KRAS)-mutated HCT116, nonsmall-cell-lung-cancer, A549 and TNBC, MDA-MB-231 cells. The ADCC of Fcγ-CR T cells was associated with the overexpression of EGFR on ECCs. In conclusion, CD32A131R-CR T cells are efficiently redirected by cetuximab or panitumumab against breast cancer cells overexpressing EGFR. 相似文献