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991.
Evaluation of 122 advanced‐stage cutaneous squamous cell carcinomas by comprehensive genomic profiling opens the door for new routes to targeted therapies 下载免费PDF全文
Rami N. Al‐Rohil MD Ashley J. Tarasen MD J. Andrew Carlson MD Kai Wang MD PhD Adrienne Johnson BS Roman Yelensky PhD Doron Lipson PhD Julia A. Elvin MD PhD Jo‐Anne Vergilio MD Siraj M. Ali MD PhD James Suh MD Vincent A. Miller MD Philip J. Stephens PhD Prasanth Ganesan MD Filip Janku MD PhD Daniel D. Karp MD Vivek Subbiah MD Martin C. Mihm MD Jeffrey S. Ross MD 《Cancer》2016,122(2):249-257
992.
Dorrance AM Liu S Chong A Pulley B Nemer D Guimond M Yuan W Chang D Whitman SP Marcucci G Caligiuri MA 《Blood》2008,112(6):2508-2511
The partial tandem duplication of MLL (MLL-PTD) is found in 5% to 10% of patients with acute myeloid leukemia (AML) and normal cytogenetics. Its expression in leukemic blasts is coincident with a silenced wild-type (WT) MLL allele. We therefore generated mice expressing the Mll-PTD in the absence of Mll-WT. These Mll(PTD/-) mice die at birth unlike the normal life expectancy of Mll(PTD/WT), Mll(WT/-), and Mll(WT/WT) mice. Using Mll(WT/WT) fetal liver cells (FLC) as baseline, we compared Mll(PTD/-) with Mll(PTD/WT) FLC and found both had increased HoxA gene expression and granulocyte-macrophage colony-forming progenitor cells (CFU-GM); in contrast, only Mll(PTD/WT) FLC had increased pluripotent hemopoietic progenitors (CFU-GEMM). The similarities between Mll(PTD/WT) and Mll(PTD/-) mice suggest that the Mll-PTD mutation can up-regulate target genes in a dominant, gain-of-function fashion. The differences between these 2 genotypes suggest that in select tissues the Mll-PTD requires cooperation with the Mll-WT in the genesis of the observed abnormality. 相似文献
993.
Ban K Gao Y Amin HM Howard A Miller C Lin Q Leng X Munsell M Bar-Eli M Arlinghaus RB Chandra J 《Blood》2008,111(5):2904-2908
Chronic myelogenous leukemia (CML) invariably progresses to blast crisis, which represents the most proliferative phase of the disease. The BCR-ABL1 oncogene stimulates growth and survival pathways by phosphorylating numerous substrates, including various Src family members. Here we describe up-regulation, in contrast to activation, of the ubiquitously expressed Src kinase, Fyn, by BCR-ABL1. In a tissue microarray, Fyn expression was significantly increased in CML blast crisis compared with chronic phase. Cells overexpressing BCR-ABL1 in vitro and in vivo display an up-regulation of Fyn protein and mRNA. Knockdown of Fyn with shRNA slows leukemia cell growth, inhibits clonogenicity, and leads to increased sensitivity to imatinib, indicating that Fyn mediates CML cell proliferation. In severe combined immunodeficient (SCID) mice injected with Fyn shRNA-expressing cells, myeloid-derived cell numbers dropped by 50% and death from leukemia was delayed. Taken together, these results encourage the development of therapies targeting Fyn expression. 相似文献
994.
995.
Black AT Gray JP Shakarjian MP Mishin V Laskin DL Heck DE Laskin JD 《Toxicology and applied pharmacology》2008,232(1):14-24
Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE2, PGF2α, PGD2 and PGI2 (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prostaglandin production and prostaglandin synthase expression in primary cultures of undifferentiated and calcium-differentiated mouse keratinocytes. Both cell types were found to constitutively synthesize PGE2, PGD2 and the PGD2 metabolite PGJ2. Twenty-four hours after treatment with UVB (25 mJ/cm2), production of PGE2 and PGJ2 increased, while PGD2 production decreased. This was associated with increased expression of COX-2 mRNA and protein. UVB (2.5–25 mJ/cm2) also caused marked increases in mRNA expression for the prostanoid synthases PGDS, mPGES-1, mPGES-2, PGFS and PGIS, as well as expression of receptors for PGE2 (EP1 and EP2), PGD2 (DP and CRTH2) and prostacyclin (IP). UVB was more effective in inducing COX-2 and DP in differentiated cells and EP1 and IP in undifferentiated cells. UVB readily activated keratinocyte PI-3-kinase (PI3K)/Akt, JNK and p38 MAP signaling pathways which are known to regulate COX-2 expression. While inhibition of PI3K suppressed UVB-induced mPGES-1 and CRTH2 expression, JNK inhibition suppressed mPGES-1, PGIS, EP2 and CRTH2, and p38 kinase inhibition only suppressed EP1 and EP2. These data indicate that UVB modulates expression of prostaglandin synthases and receptors by distinct mechanisms. Moreover, both the capacity of keratinocytes to generate prostaglandins and their ability to respond to these lipid mediators are stimulated by exposure to UVB. 相似文献
996.
Bandarenko N Hay SN Holmberg J Whitley P Taylor HL Moroff G Rose L Kowalsky R Brumit M Rose M Sawyer S Johnson A McNeil D Popovsky MA 《Transfusion》2004,44(11):1656-1662
BACKGROUND: The utilization of cryopreserved red blood cell (RBC) units had been limited by a maximum postdeglycerolization storage of 24 hours at 1 to 6 degrees C until the recent development of a closed system for the glycerolization and deglycerolization process. STUDY DESIGN AND METHODS: Sixty leukoreduced additive solution (AS), AS-1 (n = 30) and AS-3 (n = 30) RBC units from 500-mL whole blood (WB) collections were stored for 6 days, glycerolized, frozen at -70 +/- 5 degrees C for at least 14 days, thawed, deglycerolized, and stored for 15 days at 1 to 6 degrees C. Glycerolization and deglycerolization were performed with the ACP 215. In-vitro variables were tested before glycerolization, on Day 0, and Day 15 after deglycerolization storage. Forty donors were assessed for double-label 24-hour percent recovery, and T1/2 survival time was measured for 20 donors. RESULTS: Postdeglycerolization mean +/- standard deviation in-vitro RBC mass recoveries were 93 +/- 5 percent for AS-1 and 95 +/- 4 percent for AS-3. Mean hemoglobin +/- standard deviation after deglycerolization was 50.5 +/- 5.5g for AS-1 and 50.1 +/- 3.5g for AS-3. Mean hemolysis (Day 15) was 0.36 +/- 0.11 percent for AS-1 and 0.38 +/- 0.13 percent for AS-3. Double-label 24-hour in-vivo recoveries were 82.5 +/- 7.8 percent for AS-1 and 81.4 +/- 7.1 percent for AS-3. The 51Cr T1/2 value was 41.8 +/- 3.97 for AS-1 and 40.6 +/- 7.11 for AS-3. Other in-vitro variables were as expected. CONCLUSION: Leukoreduced AS-1 and AS-3 RBCs after frozen storage at -70 +/- 5 degrees C can be stored for up to 14 days when processing is performed with the ACP 215 system with resuspension of deglycerolized RBCs in AS-3. 相似文献
997.
Federico Scorletti Manish N. Patel Adrienne M. Hammill Kiersten W. Ricci Charles M. Myer Roshni Dasgupta 《Journal of pediatric surgery》2018,53(5):1056-1059
Background
Vascular malformations isolated to skeletal muscles are rare and often debilitating due to pain and very challenging to treat. Multi-modal management options include compression garments, medical therapy, sclerotherapy, and surgical resection.Methods
A retrospective review of patients who underwent sclerotherapy for intramuscular venous malformations (IVM) between 2008 and 2016 was performed. Demographics, indications, and clinical follow-up were analyzed.Results
Twenty patients underwent sclerotherapy for IVM. Six males and 14 females underwent 58 procedures. All patients presented with pain and were treated initially with compression garments. Median age at first treatment was 13 years (+/? 5.06 years). Initial protocol consisted of 2 sclerotherapy procedures with sodium tetradecyl sulfate (STS) within a 2–3 month interval. Median volume of the lesion was 40 cm3 (+/? 28.7), mostly located in the lower extremities (15/20). Median number of treatments was 2 (+/? 1.95). Treatment prior to puberty resulted in a median symptom-free time of 4 years (+/? 2.18), while after puberty resulted in a symptom-free time of 2 years (+/? 2.28). Two patients had an underlying coagulopathy and were admitted for observation and peri-procedural Lovenox. No procedure related complications were noted with a median follow-up of 4 years (+/? 2.27).Conclusion
IVMs are rare but can be incapacitating secondary to pain. Sclerotherapy is a useful minimally invasive procedure generally requiring at least two consecutive treatments. Treatment of patients prior to puberty appears to provide a more durable result, and surgical resection may be avoided.Type of study
retrospective.Level of evidence
IV 相似文献998.
Headley AJ 《American family physician》2003,68(2):323-328
Patients with necrotizing soft tissue infections often present initially to family physicians. These infections must be detected and treated rapidly to prevent loss of limb or a fatal outcome. Unfortunately, necrotizing soft tissue infections have no pathognomonic signs. Patients may present with some evidence of cellulitis, vesicles, bullae, edema, crepitus, erythema, and fever. They also may complain of pain that seems out of proportion to the physical findings; as the infection progresses, their pain may decrease. Magnetic resonance imaging and laboratory findings such as acidosis, anemia, electrolyte abnormalities, coagulopathy, and an elevated white blood cell count may provide clues to the diagnosis. No single organism or combination of organisms is consistently responsible for necrotizing soft tissue infections. Most infections are polymicrobial, with both anaerobic and aerobic bacteria frequently present. Fungal infections also have been reported. Generally, bacterial and toxin-related effects converge to cause skin necrosis, shock, and multisystem organ failure. Aggressive debridement of infected tissues is critical to management. Antimicrobial therapy is important but remains secondary to the removal of diseased and necrotic tissues. 相似文献
999.
Wendy C. Coates MD Cherri D. Hobgood MD Adrienne Birnbaum MD Susan E. Farrell MD 《Academic emergency medicine》2003,10(10):1113-1117
Medical school faculty members who specialize in the scholarship of teaching have unique requirements for academic advancement in universities with clinician-educator series. While excellence in teaching is the cornerstone of achievement, attention to traditional academic pursuits improves the likelihood of a favorable review by the institution's promotion and tenure committee. The teaching portfolio is an effective means to document performance. Ongoing faculty development and sound mentoring relationships facilitate the academic advancement of clinician-educators. 相似文献
1000.
Tim?NestlerEmail authorView authors OrcID profile Johannes?Huber Adrienne?M.?Laury Hendrik?Isbarn Axel?Heidenreich Hans?U.?Schmelz Christian?G.?Ruf 《World journal of urology》2018,36(6):913-920