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1.
Multimers of soluble major histocompatibility complex class I and II molecules have proven to be useful reagents in quantifying and following specific T cell populations. This study describes the design, generation, and characterization of a novel, single chain I-A(b) molecule which utilizes a unique linker derived from the murine invariant chain. A fragment of the invariant chain, residues 58-85, binds to a region proximal to the class II peptide binding groove and stabilizes occupancy of the class II invariant chain-associated peptide. We have utilized this fragment, replacing CLIP with the Ealpha peptide sequence, to lock the attached peptide into the class II binding groove. The single chain I-A(b) molecule was recognized by a panel of conformation-sensitive, I-A(b)-specific, monoclonal antibodies. Membrane-bound and soluble forms of the single chain I-A(b) stimulated an antigen-specific T cell hybridoma, and tetramers made from soluble monomers stained these cells. The unique features of this molecule may be useful in the design of recombinant T cell receptor ligands containing peptides with low affinity for MHC. 相似文献
2.
Thomas Schleeh Leszek Salamon Georg Hinrichsen Gerhard Komehl 《Macromolecular chemistry and physics.》1993,194(10):2771-2777
Blends containing poly(ethylene terephthalate) (PET) and a series of alkyloxy laterally substituted liquid-crystalline copolyesters (HTO5-X series 1 ) in various ratios were prepared in the melt at 260°C by mechanical mixing. The visual and light microscopical appearance of the blends in the solid state and in the melt was found to be homogeneous for those blends which contained an aliphatic-rich HT05-X copolyester. The homogeneous appearance can be explained by a colloidal dispersion of the liquid-crystalline polymer (LCP) in PET. Obvious phase separation in the melt occurs slowly after long periods of time. Phase separation is forced by annealing at about 270°C, where a change of viscosity is observed, and by shearing the sample. Characterization of theblends by DSC experiments shows that the thermal behaviour of all blends is dominated by the phase transitions of PET and that the LC-low-phase of the HTO5-X copolyesters with a high degree of alkyloxy substitution is suppressed. The WAXS diffraction patterns of all blends contained an amorphous halo. For blends with low HTO5-X concentration, inner reflexions from the nematic sanidic phase, as exhibited by the HTO5-X copolyester, could be observed. For blends with higher HTO5-X copolyester concentration, characteristic reflexions from HTO5-X copolyester crystals could be observed. The number of X-ray reflexions of the crystalline LCP in the blend is reduced compared to that of the pure LCP. 相似文献
3.
Fiander A Man S Borysiewicz LK Wilkinson GW 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》1997,8(5):331-338
Human papillomavirus (HPV) infection is associated with transformation and clonal expansion of infected epithelial cells, resulting in the production of a benign growth, i.e. a wart. Recently, however, HPV has emerged as the primary causative agent of cervical carcinoma, malignancy being associated with the presence of the viral genome (predominantly genotypes 16 and 18) in cancerous cells. The only HPV proteins reliably expressed in neoplastic lesions are the 'oncogenic' E6 and E7 proteins, that serve both as tumour-specific markers and potential targets for immunotherapeutic intervention. As intracellular (nuclear) proteins, the E6 and E7 gene products may be hidden from the humoral immune response. Attention has thus focused on the generation of a vaccine capable of inducing or stimulating a cellular immune response to HPV 16 and HPV 18 E6 and E7. Vaccine development has been constrained by the absence of an appropriate animal model, the oncogenic nature of E6 and E7 and technical difficulties associated with detection of cytotoxic T cell responses to these antigens. Despite these difficulties, vaccine strategies have now been devised based on immunisation with synthetic peptide, whole protein and a vaccinia virus recombinant. Phase I/II human clinical trials have been initiated, and preliminary results have demonstrated the induction of specific cellular immune responses after immunisation. The HPV-associated neoplasia in cervical cancer represents an excellent target for therapeutic intervention because the tumour-associated antigens are so clearly defined. As such, it provides an appropriate model for establishing the general principles of cancer immunotherapy in humans. 相似文献
4.
Józef Langfort Leszek Budohoski Hanna Kaciuba-Uściłko Krystyna Nazar John R. A. Challiss Eric A. Newsholme 《European journal of applied physiology》1991,62(2):145-150
Summary The effects of two types of acute exercise (1 h treadmill running at 20 m· min–1, or 6 × 10-s periods at 43 m · min–1, 0° inclination), as well as two training regimes (endurance and sprint) on the sensitivity of epitrochlearis muscle [fast twitch (FT) fibres] to insulin were measured in vitro in rats. The hormone concentration in the incubation medium producing the half maximal stimulation of lactate (la) production and glycogen synthesis was determined and used as an index of the muscle insulin sensitivity. A single period of moderate endurance as well as the sprint-type exercise increased the sensitivity of la production to insulin although the rate of la production enhanced markedly only after sprint exercise at 10 and 100 U· ml–1 of insulin. These effects persisted for up to 2 h after the termination of exercise. Both types of exercise significantly decreased the muscle glycogen content, causing a moderate enhancement in the insulin-stimulated rates of glycogen synthesis in vitro for up to 2 h after exercise. However, a significant increase in the sensitivity of this process to insulin was found only in the muscle removed 0.25 h after the sprint effort. Training of the sprint and endurance types increased insulin-stimulated rates of glycolysis 24 h after the last period of exercise. The sensitivity of this process to insulin was also increased at this instant. Both types of training increased the basal and maximal rates of glycogen snythesis, as well as the sensitivity of this process to insulin at the 24th following the last training session. It was concluded that in the epitrochlearis muscle, containing mainly FT fibres, both moderate and intensive exercise (acute and repeated) were effective in increasing sensitivity of glucose utilization to insulin. Thus, the response in this muscle type to increased physical activity differs from that reported previously in the soleus muscle, representing the slow-twitch, oxidative fibres in which sprint exercise did not produce any changes in the muscle insulin sensitivity. 相似文献
5.
The double fluorescent retrograde technique was employed to examine the distribution of the inferior olive (IO) neurones projecting to the cortex of the rostral and caudal parts of the paramedian lobule (PML) in the rabbit cerebellum, known to be the face-forelimb and hindlimb receiving areas, respectively. Moreover, this technique was also used to investigate the possibility that IO projections reaching these two somatotopically non-homologous PML regions are collaterals of the same axones. No other reports have addressed this question. After non-overlapping unilateral injections of the cytoplasmic tracer fast blue (FB) and the nuclear dye diamidino yellow (DY) into the rostral and caudal PML, respectively, numerous single FB- or DY-labelled cells were found in the defined regions of the contralateral IO. These regions showed considerable overlap, apart from the dorsal accessory olive where a clear spatial separation of labelled cell groups was observed. Furthermore, double FB + DY-labelled neurones (n = 310) were seen in the medial accessory olive, the dorsal and ventral laminas of the principal olive, in the dorsomedial cell column and the beta nucleus. It suggests that IO neurones may branch to supply the two functionally different PML regions and in this way participate in the mechanisms of forelimb-hindlimb coordination. 相似文献
6.
We examined astroglial cells in the brain of the pygmy shrew Sorex minutus (Insectivora). For that purpose we labeled glial fibrillary acidic protein (GFAP) immunohistochemically in brain sections with a polyclonal antibody. Antigen retrieval experiments were performed to counteract formaldehyde fixation masking of GFAP epitopes. Our results showed remarkable paucity of GFAP-immunoreactive cells and fibers in the cerebral cortex and nuclei, as well as in the majority of the diencephalic and mesencephalic structures. In the forebrain, significant numbers of GFAP-containing astrocytes were found only in the ependyma and subventricular zones, superficial part of layer I of the cerebral cortex, and the majority of white matter structures. In the diencephalon, habenular nuclei were rich in GFAP-immunopositive astrocytes and labeled radial fibers were extended between median eminence and the third ventricle. A considerably higher density of labeled astrocytes was detected in the caudal brainstem and cerebellum. In contrast, in the mouse brain, immunoreactive astrocytes were present in large quantities in various structures. Staining of sections of the shrew brain against glutamine synthetase revealed abundance of immunofluorescent astrocytes in many areas, especially in the shrew cerebral cortex. It seems probable that in the shrew brain only a limited fraction of astroglia expresses GFAP, while other astroglial cells can be detected with different markers. It is possible that the rodent type of astroglial GFAP expression might not be common to insectivores and probably to some other mammalian orders. 相似文献
7.
Treatment with continuous positive airway pressure may affect blood glucose levels in nondiabetic patients with obstructive sleep apnea syndrome 总被引:5,自引:0,他引:5
STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is often associated with impaired glucose metabolism. Data on the effects of OSAS treatment with continuous positive airway pressure (CPAP) on blood glucose and insulin resistance are conflicting. The study aimed at assessing the immediate effect of CPAP on glucose control measured with a continuous glucose monitoring system (CGMS). PARTICIPANTS AND MEASUREMENTS: Nine non-diabetes subjects with OSAS (mean age 53.0 +/- 8.0 years; body mass index 34.8 +/- 5.3 kg/m2) underwent 2 overnight polysomnographic examinations: a diagnostic study and one with CPAP treatment. Continuous glucose monitoring system (CGMS) was applied overnight on both occasions. Glucose metabolism was assessed with a 75-g oral glucose tolerance test, plasma insulin and homeostatic model assessment of insulin resistance (HOMA-IR) index. RESULTS: The mean (+/- SD) apnoea-hypopnea index (AHI) at diagnostic polysomnography was 54.3 +/- 29.3 (range 16-81). Fasting plasma insulin levels in patients with OSAS was 84.3 +/- 43.4 pM at baseline, and the HOMA-IR was 3.6 +/- 2.2. CPAP treatment in the subjects with OSAS resulted in a significant reduction in the AHI to 4.5 +/- 7.1. All of the major saturation parameters improved significantly on CPAP. CGMS showed mean glucose values significantly higher during the CPAP night than during the diagnostic night: 80 +/- 11 mg/dL versus 63 +/- 7 mg/dL (P < .01). Fasting insulin and HOMA-IR measured after the CPAP night tended to be higher than at baseline (98.4 +/- 51.0 pmol vs 84.3 +/- 43.4 pmol and 3.9 pmol +/- 2.6 vs 3.6 +/- 2.2 pmol, respectively, P > .05). CONCLUSION: CPAP treatment in nondiabetic obese patients with OSAS may have an immediate elevating effect on blood glucose. 相似文献
8.
Ginalski K Rychlewski L Baker D Grishin NV 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(8):2305-2310
The complete sequence of the male-specific region of the human Y chromosome (MSY) has been determined recently; however, detailed characterization for many of its encoded proteins still remains to be done. We applied state-of-the-art protein structure prediction methods to all 27 distinct MSY-encoded proteins to provide better understanding of their biological functions and their mechanisms of action at the molecular level. The results of such large-scale structure-functional annotation provide a comprehensive view of the MSY proteome, shedding light on MSY-related processes. We found that, in total, at least 60 domains are encoded by 27 distinct MSY genes, of which 42 (70%) were reliably mapped to currently known structures. The most challenging predictions include the unexpected but confident 3D structure assignments for three domains identified here encoded by the USP9Y, UTY, and BPY2 genes. The domains with unknown 3D structures that are not predictable with currently available theoretical methods are established as primary targets for crystallographic or NMR studies. The data presented here set up the basis for additional scientific discoveries in human biology of the Y chromosome, which plays a fundamental role in sex determination. 相似文献
9.
Dariusz Dudek Tomasz Rakowski Stanislaw Bartus Dawid Giszterowicz Wojciech Dobrowolski Krzysztof Zmudka Jaroslaw Zalewski Andrzej Ochala Pawel Wieja Bogdan Janus Artur Dziewierz Jacek Legutko Leszek Bryniarski Jacek S. Dubiel 《Journal of thrombosis and thrombolysis》2010,30(3):347-353
Early rapid platelet inhibition with abciximab before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is suggested as beneficial. In previous studies on early abciximab administration clopidogrel was administered in cathlab in low loading dose. We investigated the role of early abciximab administration on top of early clopidogrel 600 mg loading dose in patients with STEMI treated with PPCI. A total of 73 non-shock STEMI < 6 h patients admitted to remote hospitals with anticipated delay to PPCI < 90 min were randomly assigned to three study groups—24 pts received abciximab before transfer to cathlab (early = group EA), 27 in cathlab during PPCI (late = group LA) and in 22 abciximab administration was left to operator’s discretion during PPCI (selective = SA; given in 22.7% of patients). All patients received clopidogrel (600 mg), aspirin and heparin (70 U/kg) before transfer to cathlab. Angiography revealed more frequent infarct-related artery patency (TIMI 2 + 3: EA vs LA vs SA: 45.8 vs 18.5 vs 13.6%, P = 0.024), better myocardial tissue perfusion (MBG 2 + 3: EA vs LA vs SA: 45.8 vs 14.8 vs 13.6%, P = 0.02) in EA group in baseline angiography. There was no difference in these angiographic parameters and ECG ST-segment resolution after PPCI. In multivariate analysis early abciximab administration was an independent predictor of infarct-related artery patency in baseline angiography (OR 6.5; 95% CI 1.83–23.1; P = 0.004). Early abciximab administration before transfer for PPCI in patients with STEMI pretreated with 600 mg of clopidogrel results in more frequent infarct-related artery patency and better myocardial tissue perfusion before PPCI. 相似文献
10.
P-glycoprotein expression influences the result of 99mTc-MIBI scintigraphy in tertiary hyperparathyroidism 总被引:2,自引:0,他引:2
Chudzinski W Niderla J Lasiecka Z Wilczynski G Gornicka B Wasiutynski A Maczewska J Kobylecka M Krolicki L Durlik M Nowacka E Lazarczyk M Dziunycz P Milewski L Nawrot I Grzela T 《International journal of molecular medicine》2005,16(2):215-219
Precise localization of parathyroid glands using 99mTc-labeled hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy could be affected by various biological factors. There is increasing evidence that radiotracer retention could be controlled by members of multidrug resistance (MDR) system, especially P-glycoprotein (P-gp). Since the role of P-gp in tertiary hyperparathyroidism (T-HPTH) scintigraphic studies is poorly recognized, the aim of the study was to compare the correlation between parathyroid P-gp expression and results of their scintigraphy in T-HPTH versus primary hyperparathyroidism (P-HPTH). P-HPTH (n = 19) and T-HPTH (n = 18) patients were subjected to 99mTc-MIBI scintigraphy followed by surgical treatment. The parathyroid glands were assessed in routine hematoxylin-eosin staining and P-gp expression was analyzed using immunohistochemistry. Parathyroids collected during cadaver donor multi-organ harvesting were used as a control. It has been found that P-HPTH-derived parathyroid glands with predominating adenoma morphology expressed less P-gp, as compared to P-gp-rich T-HPTH glands, mainly displaying nodular or diffused hyperplasia phenotype. This finding reversely correlated with results of 99mTc-MIBI scintigraphy. However, we did not observe any difference in P-gp expression nor scintigraphy result between nodular or diffused hyperplasia. Altogether, these data suggest that P-gp overexpression in T-HPTH could be responsible for decreased sensitivity of 99mTc-MIBI scintigraphy in those patients. Therefore, the recently proposed reduced neck exploration or limited parathyroid resection on the basis of scintigraphy could create the risk of persisted/recurrent hyperparathyroidism. However, this problem requires further study. 相似文献