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21.
Iodine-123-labelled fatty acids for myocardial single-photon emission tomography: current status and future perspectives 总被引:5,自引:5,他引:0
F. F. Knapp Jr. J. Kropp 《European journal of nuclear medicine and molecular imaging》1995,22(4):361-381
Renewed interest in the clinical use of iodine-123-labelled fatty acids is currently primarily focused on the use of iodine-123-labelled 15-(p-iodophenyl)pentadecanoic acid (IPPA) and modified fatty acid analogues such as 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) which show delayed myocardial clearance, thus permitting single-photon emission tomographic imaging. Interest in the use of BMIPP and similar agents results from the differences which have often been observed in various types of heart disease between regional myocardial uptake patterns of [123I]BMIPP and flow tracer distribution. Although the physiological basis is not completely understood, differences between regional fatty acid and flow tracer distribution may reflect alterations in important parameters of metabolism which can be useful for patient management or therapy planning. These tracers may also represent unique metabolic probes for correlation of energy substrate metabolism with regional myocardial viability. The two agents currently most widely used clinically are123I-labelled IPPA and BMIPP. While [123I]IPPA is commercially available as a radiopharmaceutical in Europe (Cygne) and Canada (Nordion), multicenter trials are in progress in the United States as a prelude to approval for broad use. [123I]BMIPP was recently introduced as Cardiodine for commercial distribution in Japan (Nihon Medi-Physics, Inc.). [123I]BMIPP is also being used in clinical studies on an institutional approval basis at several institutions in Europe and the United States. In this review, the development of a variety of radioiodinated fatty acids is discussed. The results of clinical trials with [123I]IPPA and [123I]BMIPP are discussed in detail, as are the future prospects for fatty acid imaging. 相似文献
22.
D. W. P. Hay Mark A. Luttmann Roseanna M. Muccitelli Roy G. Goldie 《Naunyn-Schmiedeberg's archives of pharmacology》1999,359(5):404-410
Tension and phosphatidyl inositol (PI) turnover experiments were conducted to investigate the receptors and signal transduction
pathways responsible for contractions elicited by endothelin (ET) ligands in human bronchus. Nicardipine (1 μM), the L-type
calcium channel inhibitor, or incubation in Ca2+-free medium, produced marked inhibition of contractions to the ETB receptor-selective agonist, sarafotoxin S6c, and especially those induced by KCl. In contrast, Ca2+-free medium was without appreciable effect against contraction produced by endothelin-1 (ET-1), the non-selective ETA and ETB receptor agonist. In Ca2+-free medium, ryanodine (10 μM), which inhibits intracellular calcium mobilization, reduced sarafotoxin S6c- and ET-1-induced
responses, but was without effect on responses to KCl. Similarly, nickel chloride (Ni2+; 1 mM) caused marked inhibition of contractions induced by sarafotoxin S6c or ET-1, but had no significant effect on KCl
concentration-response curves. The mixed ETA/ETB receptor antagonist SB 209670 (3 μM) inhibited responses to sarafotoxin S6c and ET-1 such that concentration-response curves
were shifted rightward, at the 30% maximum response level, by 10.0- and 3.8-fold, respectively, whereas BQ-123 (3 μM), the
ETA receptor antagonist, was without effect on responses induced by either agonist. ET-1 (1 nM–0.3 μM) caused a concentration-dependent
stimulation of PI turnover, whereas sarafotoxin S6c (0.3 nM–0.1 μM) induced only small and variable increases, except at the
highest concentration. The increase in PI turnover evoked by ET-1 was inhibited by SB 209670 (3 μM), and also by BQ-123 (3
μM). This is consistent with linkage of ETA receptors to activation of inositol phosphate generation in human bronchial smooth muscle cells. Collectively, the data suggest
that differences exist in the relative contributions of intracellular and extracellular Ca2+ mobilization mechanisms elicited by ETA and ETB receptor activation. Thus, sarafotoxin S6c-induced, ETB receptor-mediated contraction in human bronchial smooth muscle appears to be dependent, in part, upon extracellular Ca2+, although a significant component of the response was also mediated by intracellular Ca2+ release, including from ryanodine-sensitive stores. ETA receptor-mediated contraction of human airway smooth muscle was activated largely via the release of intracellular Ca2+.
Received: 21 July 1998 / Accepted: 26 January 1999 相似文献
23.
Rationale: Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect. Therefore, it is
relevant to study both postsynaptic D2-receptor and presynaptic dopamine transporter (DAT) densities among alcoholics. Objective: We investigated DAT densities, along with striatal and extrastriatal dopamine D2-receptor densities, in nine non-violent late-onset male alcoholics, who had no major mental disorder nor antisocial personality
disorder (ASPD), and nine healthy controls. Methods: [123I]PE2I and [123I]epidepride were used in SPECT imaging. Results: DAT occupancy ratios (striatum/cerebellum) were significantly lower among alcoholics than in controls. Extrastriatal D2-receptor occupancy ratios (temporal pole/cerebellum) were not significantly different between the groups. Conclusions: Striatal presynaptic DAT densities are decreased among type 1 alcoholics, and this finding is not associated with recent
alcohol abuse.
Received: 22 March 1999 / Final version: 25 June 1999 相似文献
24.
Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer 总被引:4,自引:2,他引:2
Frank Grünwald Axel Schomburg Hans Bender Edzard Klemm Christian Menzel Thomas Bultmann Holger Palmedo Jürgen Ruhimann Beate Kozak Hans-Jürgen Biersack 《European journal of nuclear medicine and molecular imaging》1996,23(3):312-319
Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with131I) and a negative FDG PET, in four cases131I-negative lymph node metastases were detectable with PET. Even in the patients with concordant staging, differences between131I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of131I-positive/FDG-negative,131I-negative/FDG-positive and131I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours131I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS. 相似文献
25.
Leonie J. M. Rijks Gerard J. Boer Erik Endert Kora de Bruin Jan C. van den Bos Peter A. P. M. van Doremalen Willem G. E. J. Schoonen Anton G. M. Janssen Eric A. van Royen 《European journal of nuclear medicine and molecular imaging》1996,23(3):295-307
We studied the potential of both stereoisomers of 17-[123I]iodovinyloestradiol (E- andZ-[123I]IVE) and of 11-methoxy-17-[123I]iodovinyloestradiol (E-andZ-[123I]MIVE) as suitable radioligands for the imaging of oestrogen receptor(ER)-positive human breast tumours. The 17-[123I]iodovinyloestradiols were prepared stereospecifically by oxidative radio-iododestannylation of the corresponding 17-tri-n-butylstannylvi-nyloestradiol precursors. Competitive binding studies were performed in order to determine the relative binding affinity (RBA) of the unlabelled 17-iodovinyloes-tradiols for the ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their123I-labelled analogues were studied in immature female rats. All four 17-iodovi-nyloestradiols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreasing potency: RBA of DES >Z-IVE >Z-MIVE >E-MIVE E-IVE. Neither of these 17-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasma. The biodistribution studies showed ER-mediated uptake in the uterus, ovaries and pituitary, that ofE- andZ-[123I]MIVE being higher than that ofE- andZ-[123I]IVE. High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24 h), were exhibited by both isomers of [123I]MIVE. The uterus-to-blood uptake ratio was higher forE-[123I]MIVE. However, the uterus-to-fat uptake ratio appeared to be higher for theZ-isomer of [123I]MIVE, especially at 24 h after injection. Metabolic properties and temperature effects, which play a more important role in vivo, probably cause the discrepancies seen between in vitro and in vivo binding results. On the basis of their in vitro binding properties and in vivo distribution characteristics we conclude thatE- andZ-[123I]MIVE could be suitable radioligands for the diagnostic imaging of ER in human breast cancer. Therefore, further studies with these radioligands in mature normal and tumour-bearing rats are warranted. 相似文献
26.
Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: The optimal scan time 总被引:2,自引:0,他引:2
Yoshihiro Onishi Yoshiharu Yonekura Fumiko Tanaka Sadahiko Nishizawa Hidehiko Okazawa Koichi Ishizu Toru Fujita Junji Konishi Takao Mukai 《European journal of nuclear medicine and molecular imaging》1996,23(11):1491-1497
Delayed single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0–3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [123I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended. 相似文献
27.
Torsten Kuwert Carlo Morgenroth Burkhard Woesler Peter Matheja Stefan Palkovic Bernhard Vollet Samuel Samnick Ulrich Maasjosthusmann Hartmut Lerch Franz-Josef Gildehaus Hansdetlef Wassmann Otmar Schober 《European journal of nuclear medicine and molecular imaging》1996,23(10):1345-1353
Using single-photon emission tomography (SPET), the radiopharmaceuticall,-3-iodine-123--methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating high-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours. 相似文献
28.
L. Prat G. Torres I. Carrió M. Roca V. Riambau L. Berná M. Estorch I. Ferrer C. Garcia 《European journal of nuclear medicine and molecular imaging》1993,20(12):1141-1145
To test iodine-125 labelled low-density lipoprotein (125I-LDL), polyclonal indium-111 labelled immunoglobulin G (111In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n=14) or a hypercholesterolaemic diet (n=10) after surgery. Six weeks later the animals were injected with 200 Ci of (125I-LDL), and/or with 100 Ci of 111In-IgG or with 9 Ci of 125I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls.Significant 111In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188±0.06 versus 0.0059±0.003 in controls (P< 0.05). There was no difference in 111In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant (125I-LDL), uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024±0.0005 vs 0.0010±0.0003 in controls, P < 0.05). 125I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012±0.0004 in the abdominal aortas vs 0.0008±0.0003 in the thoracic aortas).Polyclonal IgG may accumulate in injured arteries without active atheroma formation. Inflammatory reaction at the site of the injury may cause 111In-IgG uptake independently of atheromatous plaque formation. LDL accumulation takes place only with active atheroma formation at the site of the injury. Use of labelled peptides such as endothelin-1 may provide further insight into the mechanisms of atheromatous plaque formation. 相似文献
29.
No evidence of significant activity of the multidrug resistance gene product in primary human breast cancer 总被引:3,自引:0,他引:3
S. Hegewisch-Becker F. Staib T. Löning U. Pichlmeier N. Kröger A. Reymann D. K. Hossfeld 《Annals of oncology》1998,9(1):85-93
Background: The discovery of the multidrug resistance (MDR1) gene product P-glycoprotein (P-gp) has been widely seen as an important milestone in our understanding of the mechanisms underlying the clinical phenomenon of the emergence of resistant cells. MDR1 expression has been shown for numerous solid tumors and for virtually all hematologic malignancies. Nevertheless, results regarding MDR1/P-gp expression in human breast cancer have been controversial and the results of clinical trials on modulation of P-gp activity have not been encouraging.Patients and methods: MDR1/P-gp expression and the function of the P-gp pump were investigated in 61 tumor samples from patients with primary breast cancers by multiparameter analysis using MDR1-RT-PCR, immunohistochemistry with two MAbs (UIC2 and MRK 16) and the rhodamine 123 (Rh123) efflux assay. The cellular composition of the tumor cell suspension was analyzed by using specific MAbs against the P-gp expressing lymphocyte subsets CD4, CD8 and CD56, as well as against the HER-2/neu gene product, which was used to identify breast carcinoma cells.Results: UIC2 and MRK16 revealed a staining positivity in 72% and 75% of samples, respectively. A positive MDR1-RT-PCR signal was detected in 62% of the samples. Nevertheless, no correlation between immunohistochemistry and RT-PCR could be established. Furthermore, there was no correlation between HER-2/neu expression and MDR1-RT-PCR or P-gp immunohistochemical assays. A contamination by CD8+ and CD4+ lymphocytes was established in 100% and 84% of tumor cell suspensions, respectively. As assessed by the Rh123 efflux assay CD8+ and the CD4+ lymphocytes exhibited marked P-glycoprotein activity, whereas such activity was not detectable in a single instance for the breast carcinoma cells. In MDR1-RT-PCR positive samples, contamination by CD8 lymphocytes averaged 4.3%, while the contamination of CD8 cells in the MDR1 mRNA-negative samples was only 2.4% (P = 0.007). This signal vanished after elimination of the lymphocyte subpopulations by T-cell rosetting.Conclusions: In primary breast cancer detection of MDR1 gene expression by means of RT-PCR or immunohistochemical assays is not indicative for the MDR phenotype, since there is no evidence of significant activity of the P-gp pump. 相似文献
30.
Terz Mrin Lszl Balkay Lajos Trn Zord T. Krasznai Judit Szab-Pli Zoltn Krasznai 《European journal of pharmaceutical sciences》2005,24(5):495-501
Miltefosine is a phospholipid analog that exhibits antineoplastic activity against breast cancer metastases, but its mechanism of action remains uncertain. The aim of this study was to investigate the transport mechanism for the removal of miltefosine and [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) from multidrug-resistant cells. The P-glycoprotein pump function, cell viability, and 99mTc-MIBI and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) uptakes were measured in NIH 3T3 (3T3) and NIH 3T3MDR1 G185 (3T3MDR1) mouse fibroblasts and human lymphoid B JY cells. Miltefosine treatment increased the permeability and fluidity of these tumor cells in a concentration-dependent manner. The multidrug-sensitive cells were 3-4 times more sensitive to miltefosine than the multidrug-resistant ones. The extent of 99mTc-MIBI accumulation in the P-glycoprotein-expressing cells increased in the presence of miltefosine, whereas the rhodamine123 and daunorubicin uptakes of the cells did not change significantly. In the 3T3MDR1 cells verapamil reinstated the rhodamine123 and daunorubicin accumulation, but not the 99mTc-MIBI uptake. Cyclosporin A reinstated the uptakes of 99mTc-MIBI, daunorubicin and rhodamine123 by the 3T3MDR1 cells. In a concentration-dependent manner miltefosine decreased the extents of 99mTc-MIBI, rhodamine123, daunorubicin and 18FDG accumulation in the JY and 3T3 cells. Our findings indicate a common transport mechanism for 99mTc-MIBI and miltefosine, which is distinct from that for rhodamine123 and daunorubicin in MDR cells. 相似文献