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21.
Clinton F Stewart Lisa C Iacono Murali Chintagumpala Stewart J Kellie David Ashley W C Zamboni M N Kirstein Maryam Fouladi Louis G Seele Dana Wallace Peter J Houghton Amar Gajjar 《Journal of clinical oncology》2004,22(16):3357-3365
PURPOSE: To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients. PATIENTS AND METHODS: After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks. Pharmacokinetic studies were conducted on day 1 to attain a topotecan lactone area under the plasma concentration-time curve (AUC) of 120 to 160 ng/mL.h. After 10 patients were enrolled, the infusion was modified to 4 hours, with dosage individualization. RESULTS: Of 36 assessable patients, four patients (11.1%) had a complete response and six (16.6%) showed a partial response, and disease was stable in 17 patients (47.2%). Toxicity was mostly hematologic, with only one patient experiencing treatment delay. The target plasma AUC was achieved in 24 of 32 studies (75%) in the 30-minute infusion group, and in 58 of 93 studies (62%) in the 4-hour infusion group. The desired CSF topotecan exposure was achieved in seven of eight pharmacokinetic studies when the topotecan plasma AUC was within target range. CONCLUSION: Topotecan is an effective agent against pediatric medulloblastoma in patients who have received no therapy other than surgery. Pharmacokinetically guided dosing achieved the target plasma AUC in the majority of patients. This drug warrants testing as part of standard postradiation chemotherapeutic regimens. Furthermore, these results emphasize the importance of translational research in drug development, which in this case identified an effective drug. 相似文献
22.
Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation. 总被引:2,自引:0,他引:2
Hisataka Kobayashi Koen Reijnders Sean English Alexander T Yordanov Diane E Milenic Anastasia L Sowers Deborah Citrin Murali C Krishna Thomas A Waldmann James B Mitchell Martin W Brechbiel 《Clinical cancer research》2004,10(22):7712-7720
Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies. 相似文献
23.
Ernest C Borden Laurence H Baker Robert S Bell Vivien Bramwell George D Demetri Burton L Eisenberg Christopher D M Fletcher Jonathan A Fletcher Marc Ladanyi Paul Meltzer Brian O'Sullivan David R Parkinson Peter W T Pisters Scott Saxman Samuel Singer Murali Sundaram Allan T van Oosterom Jaap Verweij Jill Waalen Sharon W Weiss Murray F Brennan 《Clinical cancer research》2003,9(6):1941-1956
Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality. 相似文献
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Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G‐CSF in multiple myeloma: A pilot study 下载免费PDF全文
Aditi Shastri Anjali Budhathoki Stefan K. Barta Noah Kornblum Olga Derman Ramakrishna Battini Radha Raghupathy Amit K. Verma Paul S. Frenette Ira Braunschweig Murali Janakiram 《American journal of hematology》2017,92(10):1047-1051
Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G‐CSF resulted in improved HSC mobilization. Here, we present the results of an open‐label single‐arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G‐SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 106 CD34+ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G‐CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G‐CSF administration (D‐3) and continued taking it along with G‐CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 106 CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 106 CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G‐CSF is safe and signals improved mobilization over G‐CSF alone, providing a possible alternative means of mobilization that needs further investigation. 相似文献
26.
Ashok Kumar Reddy Upputuri Brahmaiah Nitesh Narayen Ravi Kumar Reddy Rupak Kumar Reddy Meghraj Chitta Srinivas Prasad Rishi Swarup Syed Maaz Mohiuddin Madhukar Reddy Murali K. Aasuri B. S. R. Murthy Milind Bhide Sajid Ahmed 《International ophthalmology》2013,33(3):251-254
To compare the blood agar (BA), sabouraud dextrose agar (SDA) and chocolate agar (CA) for the isolation of fungi in patients with mycotic keratitis. Corneal Scrapings of 229 patients with clinically diagnosed microbial keratitis were inoculated on BA, SDA, CA. The culture media were evaluated for the rate and time taken for the fungal growth. Seventy six of 229 patients had fungal keratitis. Fungus grew on BA in 60/76(78.9 %), on SDA in 76/76 (100 %), on CA in 40/76(52.6 %) patients. The fungi which grew on BA (60/76) also grown on SDA at the same time. The colony morphologies of different fungi were better on SDA than BA/CA. Among the different culture media, SDA is essential for the isolation fungi in patients with mycotic keratitis. 相似文献
27.
Gleason grade 4 prostate adenocarcinoma patterns: an interobserver agreement study among genitourinary pathologists 下载免费PDF全文
Charlotte F Kweldam Daan Nieboer Ferran Algaba Mahul B Amin Dan M Berney Athanase Billis David G Bostwick Lukas Bubendorf Liang Cheng Eva Compérat Brett Delahunt Lars Egevad Andrew J Evans Donna E Hansel Peter A Humphrey Glen Kristiansen Theodorus H van der Kwast Cristina Magi‐Galluzzi Rodolfo Montironi George J Netto Hemamali Samaratunga John R Srigley Puay H Tan Murali Varma Ming Zhou Geert J L H van Leenders 《Histopathology》2016,69(3):441-449
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The distal radio-ulnar joint can be a source of ulnar-sided wrist pain. The complex anatomy in this region of the wrist can make diagnosis of distal radio-ulnar joint problems challenging. An understanding of the anatomy can aid an accurate diagnosis. An overview of the anatomy, biomechanics and conditions of the distal radio-ulnar joint is provided, together with other common causes of ulnar-sided wrist pain. 相似文献