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51.
The ability to transplant human tumors into athymic nude mice allows studies of tumor cells in vivo. However, after s.c. injection the incidence of tumor and metastases in nude mice is frequently low. We have studied the tumorigenicity in nude mice of estradiol (E2)-sensitive breast adenocarcinoma MCF7 cells. Matrigel, an extract of basement membrane proteins, induces rapid tumor development after s.c. injection of MCF7 cells. In the absence of this matrice, MCF7 cells failed to induce tumor growth. In this in vivo model, MCF7 cells were analysed for their E2 sensitivity. Two weeks after inoculation in the presence of matrigel, cells formed growing tumors in intact mice supplemented with E2. In ovariectomized or untreated mice, tumor appearance was delayed and the growth level was very low. Thus, MCF7 cells formed tumors in the absence of E2 but retained in vivo their responsiveness to estrogen. Growing human tumors in nude mice provides a rapid and useful model for testing the sensitivity of cells to hormone. 相似文献
52.
Blinded histopathological characterisation of POLE exonuclease domain‐mutant endometrial cancers: sheep in wolf's clothing
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Inge C Van Gool Jef E H Ubachs Ellen Stelloo Cor D de Kroon Jelle J Goeman Vincent T H B M Smit Carien L Creutzberg Tjalling Bosse 《Histopathology》2018,72(2):248-258
Aims
POLE exonuclease domain mutations identify a subset of endometrial cancer (EC) patients with an excellent prognosis. The use of this biomarker has been suggested to refine adjuvant treatment decisions, but the necessary sequencing is not widely performed and is relatively expensive. Therefore, we aimed to identify histopathological and immunohistochemical characteristics to aid in the detection of POLE‐mutant ECs.Methods and results
Fifty‐one POLE‐mutant endometrioid, 67 POLE‐wild‐type endometrioid and 15 POLE‐wild‐type serous ECs were included (total N = 133). An expert gynaecopathologist, blinded to molecular features, evaluated each case (two or more slides) for 16 morphological characteristics. Immunohistochemistry was performed for p53, p16, MLH1, MSH2, MSH6, and PMS2. POLE‐mutant ECs were characterised by a prominent immune infiltrate: 80% showed peritumoral lymphocytes and 59% showed tumour‐infiltrating lymphocytes, as compared with 43% and 28% of POLE‐wild‐type endometrioid ECs, and 27% and 13% of their serous counterparts (P < 0.01, all comparisons). Of POLE‐mutant ECs, 33% contained tumour giant cells; this proportion was significantly higher than that in POLE‐wild‐type endometrioid ECs (10%; P = 0.003), but not significantly different from that in serous ECs (53%). Serous‐like features were as often (focally) present in POLE‐mutant as in POLE‐wild‐type endometrioid ECs (6–24%, depending on the feature). The majority of POLE‐mutant ECs showed wild‐type p53 (86%), negative/focal p16 (82%) and normal mismatch repair protein expression (90%).Conclusions
A simple combination of morphological and immunohistochemical characteristics (tumour type, grade, peritumoral lymphocytes, MLH1, and p53 expression) can assist in prescreening for POLE exonuclease domain mutations in EC, increasing the probability of a mutation being detected from 7% to 33%. This facilitates the use of this important prognostic biomarker in routine pathology. 相似文献53.
Mechanism and Kinetics of Factor VIII Inactivation: Study With an IgG4 Monoclonal Antibody Derived From a Hemophilia A Patient With Inhibitor 总被引:5,自引:5,他引:5
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54.
Knowles NJ He J Shang Y Wadsworth J Valdazo-González B Onosato H Fukai K Morioka K Yoshida K Cho IS Kim SM Park JH Lee KN Luk G Borisov V Scherbakov A Timina A Bold D Nguyen T Paton DJ Hammond JM Liu X King DP 《Emerging infectious diseases》2012,18(3):499-501
Foot-and-mouth disease (FMD) outbreaks recently affected 2 countries (Japan and South Korea) in eastern Asia that were free of FMD without vaccination. Analysis of viral protein 1 nucleotide sequences indicated that FMD serotype A and O viruses that caused these outbreaks originated in mainland Southeast Asia to which these viruses are endemic. 相似文献
55.
L. Michiels B. François J. Raus C. Vandevyver 《Journal of inherited metabolic disease》1996,19(6):735-738
Summary A system of five sets of multiplex polymerase chain reaction amplifications followed by denaturing gel electrophoresis analysis allows rapid analysis of all 13 exons of the phenylalanine hydroxylase gene. 相似文献
56.
Telera S Carapella CM Caroli F Crispo F Cristalli G Raus L Sperduti I Pompili A 《Neurosurgical review》2012,35(1):67-83
The paper describes a retrospective study of a consecutive series of 20 midline anterior cranial fossa meningiomas (five of
the olfactory groove, 14 of the tuberculum sellae, and one clinoidal), which were operated on via a supraorbital keyhole approach
between 2002 and 2008. The series includes three males and 17 females (mean age 57 years, mean size of the tumors 3.5 × 3 cm,
and mean follow-up 48 months). Gross total excision was achieved in 18 cases and subtotal resection in two. Out of 14 patients
with visual deficits, nine patients improved, one remained stable, and three deteriorated. Two patients presented a recurrence
3 years after surgery. One peri-operative death was recorded. The subgroup of patients with tuberculum sellae meningiomas
was analyzed in details. A meta-analysis of the major series of such meningiomas in the last 20 years has been performed in
order to compare results of different surgical techniques. With regard to primary outcomes of these tumors, gross total removal,
restoration of visual function, morbidity, mortality, and recurrence rates, the supraorbital approach, for selected cases,
seems to offer valuable results, comparable with those reported in conventional and endoscopic approaches and with very low
surgical aggressiveness. However, statistical data available from the literature, particularly on visual function, are still
too limited to draw definitive conclusions. The best surgical option for the individual patient cannot yet be standardized
and should be chosen on the basis of tumor anatomy, pre-operative clinical symptoms, and surgeon’s experience. 相似文献
57.
Marc Francois Eric Snoeckx Peter Putteman Fons Wouters Eddy De Proost Urbain Delaet Jef Peeters Marcus E. Brewster 《The AAPS journal》2003,5(1):50-54
The development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-β-cyclodextrin (HPβCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPβCD. After pH adjustment, the itraconazole/HPβCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPβCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis. 相似文献
58.
59.
S M Rybak H R Hoogenboom H M Meade J C Raus D Schwartz R J Youle 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(8):3165-3169
The construction and expression of a chimeric gene encoding a mouse/human antibody to the human transferrin receptor fused to the gene for angiogenin, a human homolog of pancreatic RNase, are described. F(ab')2-like antibody-enzyme fusions were prepared by linking the gene for human angiogenin to a chimeric anti-transferrin receptor heavy chain gene. The antibody-enzyme fusion gene was introduced into a transfectoma that secretes the chimeric light chain of the same antibody, and cell lines were cloned that synthesize and secrete the antibody-enzyme fusion protein of the expected size at a concentration of 1-5 ng/ml. Culture supernatants from clones secreting the fusion protein caused inhibition of growth and protein synthesis of K562 cells that express the human transferrin receptor but not toward a non-human-derived cell line that lacks this receptor. Whereas excess antibody to the same receptor did not itself inhibit protein synthesis, it was able to completely prevent the protein synthesis inhibition caused by the fusion protein. These results indicate that the cytotoxicity is due to a transferrin receptor-mediated mechanism involving the angiogenin portion of the fusion protein and demonstrate the feasibility of constructing recombinant antibody-RNase molecules capable of killing tumor cells bearing the transferrin receptor. The significance of the acquired cytotoxicity of a mouse/human chimeric antibody linked to a human protein may bear importantly in human therapeutic strategies that use mouse antibodies linked to toxins from plants or bacteria to target tumor cells. It is expected that the humanization of immunotoxins will lead to less toxicity and immunogenicity than currently available reagents. 相似文献
60.
Ren de Beun Ellis Jansen Rob P.W. Heinsbroek Jef L. Slangen Nanne E. van de Poll 《Psychoneuroendocrinology》1992,17(6):711-719
Male Wistar rats (N = 16) were trained to discriminate 5 μg/kg LHRH, injected intraperitoneally, from saline in a two-lever, food-reinforced drug discrimination procedure, with an injection-session interval of 45 min. Reliable discrimination of LHRH was acquired within 60 training sessions. Subsequent generalization tests in brain-cannulated animals showed dose-dependent and time-related partial substitution of intracerebroventricular LHRH for intraperitoneal LHRH (ventricle doses ranged from 25–400 ng, and the injection-session intervals ranged from 10–40min). These results indicate that centrally administered LHRH may serve as a dose- and time-dependent discriminative stimulus in male rats. 相似文献