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91.
Werner Maschewsky 《Sozial- und Pr?ventivmedizin》1993,38(2):71-76
Zusammenfassung Herzkreislauf-Erkrankungen sind die wichtigste Todesursache in den Industrieländern. Anders als die Krebsforschung, vernachlässigt die Herzkreislauf-Forschung bei uns toxische Wirkungen weitgehend, abgesehen von den Genussgiften Nikotin, Koffein, Alkohol, einigen Medikamenten und den (bei uns) arbeitsmedizinischen Randproblemen Schwefelkohlenstoff, Nitratester und Kohlenmonoxid. Es sind aber zahlreiche kardiovaskulärtoxische Arbeitsstoffe bekannt: neben den Genannten auch organische Lösemittel, Metalle, Pestizide, Vinylchlorid, polychlorierte Biphenyle, etc. Ebenso sind verschiedene toxische Wirkmechanismen auf das Herzkreislaufsystem bekannt: z. B. langfristige Entstehung von Arteriosklerose, Bluthochdruck, koronaren Herzerkrankungen, Herzmuskelerkrankungen und Herzrhythmusstörungen. Die Vernachlässigung kardiovaskulär-toxischer Wirkungen widerspricht der Logik; bei vielen Herzkreislauf-Erkrankungen ist eine toxische Mitverursachung plausibel; mit einer weiteren Aufdeckung kardiovaskulär-toxischer Wirkungen ist zu rechnen.
Summary Cardiovascular diseases are the most important cause of mortality in industrialised countries. Contrary to cancer research, cardiovascular research mostly ignores toxic effects, apart from nicotine, caffeine, alcohol, a few pharmaceutical drugs, and the (in our countries) minor workplace problems carbon disulfide, nitrate esters, and carbon monoxide. But many workplace chemicals are known to be harmful to the cardiovascular system: beside the mentioned, also organic solvents, metals, pesticides, vinylchloride, polychlorinated biphenyles, etc. Several toxic mechanisms in the cardiovascular system are already known: e.g., long-term development of atherosclerosis, hypertension, coronary heart disease, cardiomyopathy, and arrhythmia. To neglect cardiovascular toxicity is contrary to logic; for many cardiovascular diseases toxic effects may be constitutive; more of these effects may be seen in the future.
Résumé Les maladies cardiovasculaires sont les causes de mort les plus fréquentes dans les pays industrialisés. Contrairement à la recherche sur le cancer, la recherche cardiovasculaire chez nous néglige largement les effets toxiques, à part la nicotine, la caféine, l'alcool, quelques médicaments et les problèmes (chez nous) marginaux de médecine du travail tels que le sulfure de carbone, les esters de nitrate et le monoxyde de carbone. Beaucoup de substances rencontrées sur le lieu de travail sont pourtant connues pour être toxiques pour le système cardiovasculaire: celles déjà citées, les solvants organiques, les métaux, les pesticides, le chlorure de vinyl, les biphényles polychlorés, etc. Plusieurs mécanismes d'action toxique sur le système cardiovasculaires sont également connus, par exemple la formation à longue échéance d'artériosclérose, d'hypertension artérielle, de coronopathies, de cardiomyopathies, de troubles du rythme cardiaque. Négliger la toxicité cardiovasculaire est illogique; les effets toxiques pourraient contribuer à la genèse de beaucoup de maladies cardiovasculaires; la découverte d'autres effets toxiques cardiovasculaires est à prévoir.相似文献
92.
The aims of the present investigation were (a) to evaluate the effect of eccentric quadriceps training in patients with unilateral patellofemoral pain and (b) to compare the effect of eccentric and concentric quadriceps training in patients with bilateral patellofemoral pain. Fifteen patients (9 male and 6 female, aged 17–36 years with a mean of 27.5 years) participated in this study. Nine patients had unilateral pain and trained their painful leg eccentrically, while six had bilateral pain and trained one leg eccentrically and the other concentrically. Quadriceps muscle training was performed on a Kin-Com dynamometer at 90°/s and 120°/s angular velocity twice a week for 8 weeks. Before and after the treatment period the thigh muscle torques were measured on the Kin-Com dynamometer at 60°/s, 90°/s, 120°/s and 180°/s for quadriceps and at 60°/s and 180°/s for hamstrings. Nine controls, matched for gender and age with the group with unilateral pain, were tested in the same way on the Kin-Com dynamometer. For functional evaluation a knee score was calculated before training, after 8 weeks of training and at a mean of 3.4 years after completion of the training. After 8 weeks of training and at follow-up times of 1 and 3.4 years the patients were also questioned regarding whether or not they felt improvement from the training programme. To determine the degree of knee pain during the training Borg's pain scale was used. The results showed that, compared with the controls, the patients had a significantly lower knee extensor torque in their painful leg at all velocities measured. The greatest difference was found during eccentric actions. However, in comparison with the controls there were no significant differences in eccent ic and concentric knee flexor torques. After training there was a significant increase particularly in eccentric but also in concentric torque of the knee extensor in the painful leg of the eccentrically trained group. Of the six patients in the bilateral training group there were five who increased their concentric knee extensor torque and three who increased their eccentric torque. There were no significant differences in concentric and eccentric knee flexor torques before and after training in either of the legs in both training groups. The hamstring/quadriceps ratio was significantly higher in the patients' painful leg before training. However, due to increased quadriceps strength the hamstring/quadriceps ratio dropped after training. Patients in both groups reported no pain or mild pain during the training sessions. The eccentrically trained group was significantly improved both after 8 weeks of treatment and at follow-up 3.4 years later as evaluated using the knee score. The bilaterally trained group was significantly improved 3.4 years after completion of the training programme as evaluated using the knee score. 相似文献
93.
Summary Epidermal growth factor (EGF) has been shown to stimulate DNA synthesis and cell division in normal glia. At least half of malignant human gliomas (MHG) express high levels of the EGF receptor (EGFR), which are above those detected in normal brain. The demonstration that antibodies against the EGFR inhibit the growth of squamous cell carcinoma line A-431, with large numbers of EGFR, in vitro and in vivo raises the possibility that these agents could be used therapeutically against malignant human gliomas either alone or conjugated to other agents. We have measured the growth effects of EGF and an anti-EGFR monoclonal antibody, 528 (Ab-528), on four well-characterized human malignant glioma cell lines, D-263 MG, D-247 MG, U-343 MGa Cl 26, and D-37 MG, with 2.9×104, 1.5×105, 8.6×105 and 1.59×106 EGFRs per cell, respectively. EGF significantly increased cell number in D-263 MG and D-37 MG by 65% and 74%, respectively, had no effect on D-247 MG, and significantly decreased cell number in U-343 MGa Cl 26 by 39%. U-343 MGa Cl 26 growth was inhibited 19% by Ab-528, but Ab-528 had no effect on growth of the other MHG lines. Ab-528 significantly inhibited all EGF-mediated growth effects. These studies demonstrate that, although Ab-528 alone has little antiproliferative activity on MGH, it successfully competes with EGF to reduce the biological effects of EGF-EGFR binding. Therefore, this antibody could potentially be used to target radioisotopes to MHG via the EGFR for diagnosis and therapy.Supported by Grants CA-11898, NS-20023, CA-43722, and the Association for Brain Tumor Research (MHW, PAH) 相似文献
94.
It has been demonstrated in transgenic mice that the overexpression of human phospholipase A2 group IIA (sPLA2), an acute-phase reactant, is associated with depressed plasma cholesterol levels, altered lipoprotein compositions, and increased lipid depositions in aortic walls. It was the aim of the present study to investigate whether the reduced plasma cholesterol levels in sPLA2-transgenic mice may be due to an increased transfer of lipids from sPLA2-modified lipoproteins to the liver and/or other nonvascular tissues. Ten sPLA2-transgenic mice and an equal number of nontransgenic littermates were fed a cholesterol-enriched (1%) diet for 13 weeks. After autopsy, cholesterol and triglyceride concentrations were measured in homogenates of liver, spleen, kidney, and myocardial tissues. Compared to the nontransgenic controls, the sPLA2-transgenic mice exhibited significantly lower plasma cholesterol levels, which was due to a reduction in both HDL and beta-lipoprotein (LDL + beta-VLDL) cholesterol. Liver tissues from the transgenic mice were found to contain significantly increased concentrations of free and esterified cholesterol, which was not associated with increased triglyceride concentrations. Spleen, kidney, and heart tissues of the two animal groups showed no significant differences in cholesterol or triglyceride concentrations. The findings suggest that the overexpression of human secretory phospholipase A2 group IIA leads to an enhanced delivery of cholesterol from phospholipolysed lipoproteins to the liver. This mechanism is likely to contribute to the development of hypocholesterolemia observed in patients with inflammatory diseases. 相似文献
95.
James Deschner Birgit Rath-Deschner Susanne Reimann Christoph Bourauel Werner Gtz Soeren Jepsen Andreas Jger 《Annals of anatomy》2007,189(4):326-328
Recent studies have revealed that dynamic biomechanical forces can exert antiinflammatory and antiproteolytic effects on fibrocartitage. Whether the effects of mechanical strain also involve stimulation of the insulin-like growth factor (IGF) system and, therefore, of growth and repair of fibrocartilage has yet to be determined. The objective of this in vitro study was to determine if continuous biophysical strain regulates the gene expression of IGF1, IGF2, IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), and IGF-binding proteins (IGFBP) 3 and 5 in cells from the fibrocartilaginous disc of the temporomandibular joint (TMJ). Rat TMJ disc cells were subjected to continuous biophysical strain (3% and 20%) for 4 and 24 h. Subsequently, RNA was extracted and real-time PCR was performed using an iCycler iQ detection system to analyze the gene expression of the IGF system. The gene expression of IGF1, IGF2, IGF1R, IRS1, IGFBP3, and IGFBP5 was significantly (p < 0.05) inhibited when cells were subjected to continuous biophysical strain, as compared to control at both time points. High strain induced a stronger inhibition of these molecules as compared to strain of Low magnitude. In conclusion, continuous biophysical strain seems to downregulate the expression of the IGF system and may, therefore, reduce the potential of fibrocartilage for growth and repair. 相似文献
96.
Dr. Hilde van Meurs-van Woezik Hans Werner Klein Piet Krediet 《Virchows Archiv : an international journal of pathology》1980,386(3):303-316
Summary In a post mortem material of 17 cases of transposition of the great arteries (TGA) from patients with an age range from birth to two years and ten months after birth, the internal calibres of the great arteries and the ostia of the heart proved to be the same as in normal hearts. Furthermore, the media of the ascending aorta and pulmonary trunk showed no adaptation to the abnormal circulatory conditions in 15 cases of TGA with an age range from birth up to 51/2 months: in both great arteries the thickness of the tunica media and the packing density of its elastic fibres were the same as in normal hearts. However, adaptation of the tunica media of the pulmonary trunk to the abnormal circulatory conditions: increased media thickness, was found in the two remaining cases, older than 12 months.In 7 cases of pulmonary atresia (age from 1 day to 12 months) and in 9 cases of aortic atresia (age from 2 days to 37 days) the following observations were made. Vessels with reduced or absent function (ascending aorta in aortic atresia and pulmonary trunk in pulmonary atresia) showed a markedly different structure. In aortic atresia the internal calibre and thickness of the media of the ascending aorta were markedly reduced, whereas the packing density of the elastic fibres of the media remained the same as in normal hearts. In pulmonary atresia the pulmonary trunk showed large variations in internal calibre, whereas both media thickness and the packing density of its elastic fibres remained the same as in normal hearts. When the markedly enlarged single functional vessels (the pulmonary trunk in aortic atresia and the ascending aorta in pulmonary atresia) were compared no significant differences between their internal calibre, media thickness and the packing density of the elastic fibres were found indicating similar adaptation to the abnormal but comparable functional load of acting as sole arterial trunk.We are indebted to Prof. Dr. J. Moll for his help, to Dr. J.J. Willemse for statistical calculations, to Mr. P. Zondervan, M.D. (Dept. of Pathology I), for supply of material and to Mrs. L. Silvis for histo-technical assistance 相似文献
97.
Emerging paradigms of T-cell co-stimulation 总被引:3,自引:0,他引:3
The analysis of recent data reveals that T-cell co-stimulation is a hierarchical process with elements of mutual interdependence between individual co-stimulators. The expression and function of co-stimulatory molecules is biased on various T-cell subsets and is dependent on the T-cell differentiation state. The classical paradigm of T-cell co-stimulation by professional antigen-presenting cells has to incorporate the newly recognized concept of T-cell co-stimulation in the interaction with peripheral tissues, such as endothelial or epithelial cells. The two signal paradigm of T-cell co-stimulation is being replaced by a multisignal integration concept of central and peripheral co-stimulation. 相似文献
98.
Chwieralski CE Schnurra I Thim L Hoffmann W 《American journal of respiratory cell and molecular biology》2004,31(5):528-537
Injured areas of the respiratory epithelium are subject to rapid repair by the migration of adjacent epithelial cells, a process termed "restitution". Rapid re-epithelialization is promoted by interactions between migrating cells and the extracellular matrix proteins. Furthermore, epidermal growth factor (EGF) as well as trefoil factor family (TFF) peptides are well known regulators of epithelial restitution due to their motogenic effects. Migration of the human bronchial epithelial cell line BEAS-2B in modified Boyden chambers was used as a model system for airway restitution. EGF or recombinant human TFF2 or TFF3 showed mainly chemotactic activity. The motogenic response was strictly dependent upon a haptotactic substrate, but to different degrees. EGF induced phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, c-Jun-N-terminal kinase, p38, Akt, and p70S6K in BEAS-2B cells. Using specific inhibitors, the signaling cascades responsible for the motogenic response were shown to differ drastically when EGF was compared with TFF2. The motogenic effect of TFF2 was previously demonstrated to depend on ERK1/2 and protein kinase C activation; whereas the EGF-triggered motogenic response was completely independent of ERK1/2 activation but sensitive to the inhibition of phosphoinositide 3-kinase, p38, protein kinase C, or nuclear factor kappaB. However, the motogenic effects of EGF and TFF2 are additive. These data suggest that luminal EGF and TFF peptides can act synergistically in the human respiratory epithelium to enhance rapid repair processes in the course of diseases such as asthma. 相似文献
99.
Walcher P Mayr UB Azimpour-Tabrizi C Eko FO Jechlinger W Mayrhofer P Alefantis T Mujer CV DelVecchio VG Lubitz W 《Expert review of vaccines》2004,3(6):681-691
The bacterial ghost (BG) platform system is a novel vaccine delivery system endowed with intrinsic adjuvant properties. BGs are nonliving Gram-negative bacterial cell envelopes which are devoid of their cytoplasmic contents, yet maintain their cellular morphology and antigenic structures, including bioadhesive properties. The main advantages of BGs as carriers of subunit vaccines include their ability to stimulate a high immune response and to target the carrier itself to primary antigen-presenting cells. The intrinsic adjuvant properties of BGs enhance the immune response to target antigens, including T-cell activation and mucosal immunity. Since native and foreign antigens can be carried in the envelope complex of BGs, combination vaccines with multiple antigens of diverse origin can be presented to the immune system simultaneously. Beside the capacity of BGs to function as carriers of protein antigens, they also have a high loading capacity for DNA. Thus, loading BGs with recombinant DNA takes advantage of the excellent bioavailability for DNA-based vaccines and the high expression rates of the DNA-encoded antigens in target cell types such as macrophages and dendritic cells. There are many spaces within BGs including the inner and outer membranes, the periplasmic space and the internal lumen which can carry antigens, DNA or mediators of the immune response. All can be used for subunit antigen to design new vaccine candidates with particle presentation technology. In addition, the fact that BGs can also carry piggyback large-size foreign antigen particles, increases the technologic usefulness of BGs as combination vaccines against viral and bacterial pathogens. Furthermore, the BG antigen carriers can be stored as freeze-dried preparations at room temperature for extended periods without loss of efficacy. The potency, safety and relatively low production cost of BGs offer a significant technical advantage over currently utilized vaccine technologies. 相似文献
100.
Deckert M Lütjen S Leuker CE Kwok LY Strack A Müller W Wagner N Schlüter D 《European journal of immunology》2003,33(5):1418-1428
Under various inflammatory conditions, cell adhesion molecules are up-regulated in the central nervous system (CNS) and may contribute to the recruitment of leukocytes to the brain. In the present study, the functional role of vascular cell adhesion molecule (VCAM)-1 in Toxoplasma encephalitis (TE) was addressed using VCAM(flox/flox MxCre) mice. Neonatal inactivation of the VCAM-1 gene resulted in a lack of induction of VCAM-1 on cerebral blood vessel endothelial cells, whereas the constitutive expression of VCAM-1 on choroid plexus epithelial cells and the ependyma was unaffected; in these animals, resistance to T. gondii was abolished, and VCAM(flox/flox MxCre) mice died of chronic TE caused by a failure to control parasites in the CNS. Although leukocyte recruitment to the CNS was unimpaired, the B cell response was significantly reduced as evidenced by reduced serum levels of anti-T. gondii-specific IgM and IgG antibodies. Furthermore, the frequency and activation state of intracerebral T. gondii-specific T cells were decreased, and microglial activation was markedly reduced. Taken together, these data demonstrate the crucial requirement of VCAM-1-mediated immune reactions for the control of an intracerebral infectious pathogen, whereas other cell adhesion molecules can efficiently compensate for VCAM-1-mediated homing across cerebral blood vessels. 相似文献