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51.
Emre S Sebastian A Chodoff L Boccagni P Meyers B Sheiner PA Mor E Guy SR Atillasoy E Schwartz ME Miller CM 《The Mount Sinai journal of medicine, New York》1999,66(5-6):310-313
In liver transplant (LTx) recipients, gut-associated bacterial and fungal organisms produce significant postoperative morbidity and mortality. We sought to assess the role of selective digestive decontamination (SDD) in preventing postoperative infections in a large single-center cohort of liver recipients transplanted under two non-simultaneous protocols. In 212 consecutive patients transplanted between 1/1/91 and 7/31/92, SDD (gentamicin 80 mg, polymyxin B 100 mg, nystatin suspension 10 mL) was employed, starting after induction of anesthesia and continued until POD 21 (SDD Group). In 157 consecutive patients transplanted between 1/1/93 and 12/31/93, SDD was not used (non-SDD Group). Both groups received IV vancomycin and cefotaxime prophylaxis. All culture-positive infections within the first 30 days post-LTx were recorded and classified as bacterial or fungal. Infection-related mortality (patients who died of infectious complications without any technical complication) was recorded. Groups did not differ in patient demographics, United Network for Organ Sharing (UNOS) status, use of veno-venous bypass, total/warm ischemia, or length of ICU stay. Infections developed in fewer SDD patients (56/212; 26%) than non-SDD patients (69/157; 44%) (p<0.001). The incidence of gram-negative infection was less in the SDD group (11% vs. 26%, p<0. 001) as was gram-positive infection (16% vs. 26%, p<0.001). Among patients who developed infection, there was no difference between groups in infections per patient. Primary graft non-function (PNF) developed in 20 SDD patients (7/20 had infections) and 8 non-SDD patients (6/8 had infections) (p=0.06). There were no differences in incidence of fungal infections or of infection-related mortality between groups. In the SDD group, there were fewer abdominal (p<0. 001), lung (p<0.001), wound (p<0.01), and urinary tract infections (p<0.05). CONCLUSION: Use of SDD in liver recipients early after transplant was associated with significantly fewer infections in the early postoperative period. 相似文献
52.
53.
Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells. 总被引:14,自引:0,他引:14
Natalie Reimers Kristine Zafrakas Volker Assmann Cornelia Egen Lutz Riethdorf Sabine Riethdorf Jürgen Berger Sebastian Ebel Fritz J?nicke Guido Sauter Klaus Pantel 《Clinical cancer research》2004,10(10):3422-3428
PURPOSE: EMMPRIN (extracellular matrix metalloprotease inducer) is a glycosylated member of the immunoglobulin superfamily known to stimulate the production of matrix metalloproteases (MMPs) 1, 2, and 3 and MT1-MMP in peritumoral fibroblasts. We here evaluated whether EMMPRIN expression is related to tumor progression in human breast cancer. EXPERIMENTAL DESIGN: An immunohistochemical study using high-density tissue microarrays (n = 2222 breast cancer samples) and EMMPRIN-specific antibodies HIM6 and MEM-M6/1 was performed, and staining results were statistically correlated with various clinicopathological parameters. To analyze the putative association between EMMPRIN expression and bone marrow (BM) micrometastasis, an additional set of 55 breast tumors from patients with or without micrometastatic cells as determined with anti-cytokeratin antibody A45-B/B3 were included in our study. Cytokeratin-positive cells in BM were costained with EMMPRIN-specific antibody 1G6.2. RESULTS: Positive EMMPRIN staining correlated significantly with various histopathological risk factors (higher tumor grade, increased tumor size, negative estrogen receptor status and progesterone receptor status, and higher mitotic index) as well as decreased tumor-specific survival (log-rank, P = 0.0027). In particular, in patients > 50 years (i.e., postmenopausal women), EMMPRIN expression was an independent prognosticator as shown by Cox regression analysis (relative risk = 1.7, 95% confidence interval 1.4-4.3, P = 0.036). An involvement of EMMPRIN in tumor progression was also supported by the fact that it was expressed on approximately 90% of micrometastatic cells in BM. CONCLUSIONS: EMMPRIN expression in primary tumor predicts an unfavorable prognosis in breast cancer, suggesting a crucial role of EMMPRIN in progression of human mammary carcinomas. 相似文献
54.
Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 promotes progression of non-small cell lung cancer. 总被引:7,自引:0,他引:7
Wulf Sienel Sebastian Dango Ute Woelfle Alicia Morresi-Hauf Christoph Wagener Jens Brümmer Wolf Mutschler Bernward Passlick Klaus Pantel 《Clinical cancer research》2003,9(6):2260-2266
PURPOSE: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) has recently been implicated in cancer development and progression. This study was performed to assess whether CEACAM-1 expression in primary tumors is correlated to long-term survival in patients with operable non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Primary tumors of 145 consecutive patients with completely resected NSCLC (pT(1-4) pN(0-2) M(0) R(0)) were stained immunohistochemically using the monoclonal anti-CEACAM-1 antibody 4D1/C2. The prognostic relevance of CEACAM-1 expression was evaluated by univariate Kaplan-Meier and multivariate Cox regression analysis. The median follow-up period was 72 months (range, 10-130 months). RESULTS: Normal bronchiolar epithelium present in all sections exhibited no immunostaining. In contrast, 73 tumors (50.4%) showed between 1 and 66% CEACAM-1 positive tumor cells, and 72 tumors (49.6%) exhibited even a higher percentage of positive tumor cells. A high CEACAM-1 expression rate (i.e., >/=66% positive tumor cells) was more frequent in adenocarcinomas than in squamous cell carcinomas (61.9 versus 35.7%, respectively). Multivariate Cox regression analysis demonstrated that CEACAM-1 represents an independent prognosticator for cancer-related survival (P = 0.018; relative risk, 1.8; 95% confidence interval, 1.1-2.8). Subgroup analysis revealed that a high CEACAM-1 expression rate was of significant prognostic impact in pN(1)-pN(2) patients (n = 60; P = 0.024), pT(3)-pT(4) patients (n = 22; P = 0.009), and stage IIa-IIIa patients (n = 69; P = 0.012). CONCLUSIONS: The absence of CEACAM-1 in normal lung tissue and its expression in tumor cells argues against a tumor-suppressive role of CEACAM-1 in NSCLC. The correlation between elevated CEACAM-1 expression and an unfavorable prognosis indicates rather that CEACAM-1 might promote lung cancer progression. 相似文献
55.
G. Hempel Sebastian Krümpelmann Antje May-Manke Barbara Hohenlöchter Gottfried Blaschke Heribert Jürgens Joachim Boos 《Cancer chemotherapy and pharmacology》1997,40(1):45-50
To contribute to effective and safe outpatient treatment, we investigated the metabolism of trofosfamide (Trofo) after oral
administration. We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years who were treated with 150 or 250 mg/m2 Trofo in combination with etoposide. Serum samples were collected with 13 patients after oral administration, and Trofo and
its dechloroethylated metabolites were quantified by gas chromatography. Urine samples were collected from five patients and
analyzed by same method. Ifosfamide (Ifo) was the main metabolite in serum and urine (AUCTrofo:AUCIfo 1:13), whereas cyclophosphamide (Cyclo) was formed in smaller amounts (AUCIfo:AUCCyclo 18:1). Ifo and Cyclo were further oxidized in the chloroethyl side chains to form 2- and 3-dechloroethylifosfamide in varying
quantities. The urinary excretion of Trofo and its dechloroethylated metabolites amounted to about 10% of the total dose.
Our results confirm former in vitro observations about the metabolism of Trofo. The main side-chain metabolites Ifo and Cyclo
can be further activated by oxidation and formation of their respective phosphoramide mustards. Hence, Trofo is an interesting
agent for oral chemotherapy.
Received 21 July 1996 / Accepted: 11 November 1996 相似文献
56.
The assessment of relevance of toxicological testing was compared with approaches of diagnostic medicine, a discipline that faces a comparable situation. Considering the work of a toxicologist as setting a diagnosis for compounds, assessment tools for diagnostic tests were transferred to toxicological tests. In clinical diagnostics, test uncertainty is well accepted and incorporated in this assessment. Furthermore, prevalence information is considered to evaluate the gain in information resulting from the application of a test. Several common toxicological scenarios, in which test uncertainty and prevalence are combined, are discussed including the interdependence of test accuracy, prevalence and predictive values or the sequential application of a screening and a confirmatory test. In addition, real prevalences derived from prevalences determined by an imperfect test are presented. We conclude that information on prevalences of toxic health effects is required to allow a complete assessment of the relevance of toxicological test. In this process, lessons can be learned from evidence-based approaches in clinical diagnostics. 相似文献
57.
Alessio Nencioni Lucia Wille Giovanna Dal Bello Davide Boy Gabriella Cirmena Sebastian Wesselborg Claus Belka Peter Brossart Franco Patrone Alberto Ballestrero 《Clinical cancer research》2005,11(11):4259-4265
PURPOSE: Bcl-2 overexpression is frequently detected in lymphoid malignancies, being associated with poor prognosis and reduced response to therapy. Here, we evaluated whether Bcl-2 overexpression affects the cytotoxic activity of proteasome inhibitors taken alone or in association with conventional anticancer drugs or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). EXPERIMENTAL DESIGN: Jurkat cells engineered to overexpress Bcl-2 were treated with proteasome inhibitors (MG132, epoxomicin, and bortezomib), anticancer drugs (etoposide and doxorubicin), TRAIL, or combinations of these compounds. Cell death and loss of mitochondrial transmembrane potential were detected by flow cytometry. Cytosolic relocalization of cytochrome c and SMAC/Diablo, caspase cleavage, and Bcl-2 and Mcl-1 levels were determined by immunoblotting. Nuclear factor-kappaB inhibition was done by retroviral transduction with a dominant-negative mutant of IkappaBalpha. RESULTS: Bcl-2 overexpression results in significant inhibition of apoptosis in response to proteasome inhibitors, antiblastics, and TRAIL. Addition of TRAIL to proteasome inhibitors results in a synergistic cytotoxic effect in Bcl-2-overexpressing cells, whereas this result is not reproduced by the combination of proteasome inhibitors with antiblastic drugs. Importantly, proteasome inhibitors plus TRAIL induce mitochondrial dysfunction irrespective of up-regulated Bcl-2. Bcl-2 cleavage to a fragment with putative proapoptotic activity and elimination of antiapoptotic Mcl-1 may both play a role in proteasome inhibitors-TRAIL cooperation. Conversely, nuclear factor-kappaB inhibition by proteasome inhibitors is per se insufficient to explain the observed synergy. CONCLUSIONS: Combined proteasome inhibitors and TRAIL overcome the apoptotic threshold raised by Bcl-2 and may prove useful in the treatment of chemoresistant malignancies with up-regulated Bcl-2. 相似文献
58.
Sebastian Bauer Hauke Lang Jochen Schütte J?rg Thomas Hartmann 《Journal of clinical oncology》2005,23(27):6800-1; author reply 6801-2
59.
Wanling Foo Alexander Wiede Sebastian Bierwirth Rainer Heintzmann Adrian T. Press Walter Hauswald 《Biomedical optics express》2022,13(7):3723
Research in translational medicine often requires high-resolution characterization techniques to visualize or quantify the fluorescent probes. For example, drug delivery systems contain fluorescent molecules enabling in vitro and in vivo tracing to determine biodistribution or plasma disappearance. Albeit fluorescence imaging systems with sufficient resolution exist, the sample preparation is typically too complex to image a whole organism of the size of a mouse. This article established a mesoscopic imaging technique utilizing a commercially available cryo-microtome and an in-house built episcopic imaging add-on to perform imaging during serial sectioning. Here we demonstrate that our automated red, green, blue (RGB) and fluorescence mesoscope can generate sequential block-face and 3-dimensional anatomical images at variable thickness with high quality of 6 µm × 6 µm pixel size. In addition, this mesoscope features a numerical aperture of 0.10 and a field-of-view of up to 21.6 mm × 27 mm × 25 mm (width, height, depth). 相似文献
60.
Adrienne Elisabeth van der Hoeven Rolf Fronczek Mink Sebastian Schinkelshoek Frederik Willem Cornelis Roelandse Jaap Adriaan Bakker Sebastiaan Overeem Denise Bijlenga Gert Jan Lammers 《Sleep》2022,45(5)
Study ObjectivesThe diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level ≤ 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111–200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence.MethodsRetrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands. For n = 271, we had full data on cataplexy type (“typical” or “atypical” cataplexy).ResultsCompared to those with normal hypocretin-1 levels (>200 pg/mL), a higher percentage of individuals with intermediate hypocretin-1 levels had typical cataplexy (75% or 12/16 vs 9% or 8/88, p < .05), and/or met the diagnostic polysomnographic (PSG) and Multiple Sleep Latency Test (MSLT) criteria for narcolepsy (50 vs 6%, p < .001). Of those with typical cataplexy, 88% had low, 7% intermediate, and 5% normal hypocretin-1 levels (p < .001). Atypical cataplexy was also associated with hypocretin deficiency but to a lesser extent. A hypocretin-1 cutoff of 150 pg/mL best predicted the presence of typical cataplexy and/or positive PSG and MSLT findings.ConclusionIndividuals with intermediate hypocretin-1 levels or typical cataplexy more often have outcomes fitting the PSG and MSLT criteria for narcolepsy than those with normal levels or atypical cataplexy. In addition, typical cataplexy has a much stronger association with hypocretin-1 deficiency than atypical cataplexy. We suggest increasing the NT1 diagnostic hypocretin-1 cutoff and adding the presence of clearly defined typical cataplexy to the diagnostic criteria of NT1. Clinical trial information: This study is not registered in a clinical trial register, as it has a retrospective database design. 相似文献