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991.
Blatter K Schultz W 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2006,168(4):541-546
The behavioral functions of rewards comprise the induction of learning and approach behavior. Rewards are not only related
to vegetative states of hunger, thirst and reproduction but may also consist of visual stimuli. The present experiment tested
the reward potential of different types of still and moving pictures in three operant tasks involving key press, touch of
computer monitor and choice behavior in a laboratory environment. We found that all tested visual stimuli induced approach
behavior in all three tasks, and that action movies sustained consistently higher rates of responding compared to changing
still pictures, which were more effective than constant still pictures. These results demonstrate that visual stimuli can
serve as positive reinforcers for operant reactions of animals in controlled laboratory settings. In particular, the coherently
animated visual stimuli of movies have considerable reward potential. These observations would allow similar forms of visual
rewards to be used for neurophysiological investigations of mechanisms related to non-vegetative rewards. 相似文献
992.
Pomper JK Haack S Petzold GC Buchheim K Gabriel S Hoffmann U Heinemann U 《Journal of neurophysiology》2006,95(1):355-368
Prolonged seizures, e.g., induced by fever, experienced early in life are considered a precipitating injury for the subsequent development of temporal lobe epilepsy. During in vitro epileptiform activity, spreading depressions (SDs) have often been observed. However, their contribution to changes in the properties of juvenile neuronal tissue is unknown. We therefore used the juvenile hippocampal slice culture preparation (JHSC) maintained in normoxia (20% O(2)-5% CO(2)-75% N(2)) to assess the effect of repetitive SD-like events (SDLEs) on fast field potentials and cell damage. Repetitive SDLEs in the CA1 region could be induced in about two-thirds of the investigated JHSCs (n = 61) by repetitive electrical stimulation with 2-200 pulses. SDLEs were characterized by a transient large negative field potential shift accompanied by intracellular depolarization, ionic redistribution, slow propagation (assessed by intrinsic optical signals) and glutamate receptor antagonist sensitivity. The term "SDLE" was used because evoked fast field potentials were only incompletely suppressed and superimposed discharges occurred. With 20 +/- 1 repetitive SDLEs (interval of 10-15 min, n = 7 JHSCs), the events got longer, their amplitude of the first peak declined, while threshold for induction became reduced. Evoked fast field potentials deteriorated and cell damage (assessed by propidium iodide fluorescence) occurred, predominantly in regions CA1 and CA3. As revealed by measurements of tissue partial oxygen pressure during SDLEs repetitive transient anoxia accompanying SDLE might be critical for the observed cell damage. These results, limited so far to the slice culture preparation, suggest SDs to be harmful events in juvenile neuronal tissue in contrast to what is known about their effect on adult neuronal tissue. 相似文献
993.
Ewert SD Kaiser K Kernschmidt L Wiegrebe L 《Journal of the Association for Research in Otolaryngology》2012,13(1):131-143
Interaural time differences (ITDs) can be used to localize sounds in the horizontal plane. ITDs can be extracted from either
the fine structure of low-frequency sounds or from the envelopes of high-frequency sounds. Studies of the latter have included
stimuli with periodic envelopes like amplitude-modulated tones or transposed stimuli, and high-pass filtered Gaussian noises.
Here, four experiments are presented investigating the perceptual relevance of ITD cues in synthetic and recorded “rustling”
sounds. Both share the broad long-term power spectrum with Gaussian noise but provide more pronounced envelope fluctuations
than Gaussian noise, quantified by an increased waveform fourth moment, W. The current data show that the JNDs in ITD for band-pass rustling sounds tended to improve with increasing W and with increasing bandwidth when the sounds were band limited. In contrast, no influence of W on JND was observed for broadband sounds, apparently because of listeners' sensitivity to ITD in low-frequency fine structure,
present in the broadband sounds. Second, it is shown that for high-frequency rustling sounds ITD JNDs can be as low as 30 μs.
The third result was that the amount of dominance for ITD extraction of low frequencies decreases systematically with increasing
amount of envelope fluctuations. Finally, it is shown that despite the exceptionally good envelope ITD sensitivity evident
with high-frequency rustling sounds, minimum audible angles of both synthetic and recorded high-frequency rustling sounds
in virtual acoustic space are still best when the angular information is mediated by interaural level differences. 相似文献
994.
Pneumococcal meningitis post cochlear implantation: development of an animal model in the guinea pig
In 2002 an increased number of cochlear implant related meningitis cases was reported by the U. S. Food and Drug Administration (FDA). The most commonly identified causative agent was Streptococcus pneumoniae. Although most cases of meningitis were related to a special electrode design, the risk for post-operative pneumococcal meningitis might nonetheless be enhanced by opening of the cochlea during implantation. In the present study, a threshold model for middle ear inoculation of S. pneumoniae was established in the guinea pig after cochlear implantation to assess the post-operative risk of meningitis. Guinea pigs were implanted unilaterally with a silicone cochlear implant electrode dummy. Five weeks after implantation, animals were challenged via the middle ear with a clinically relevant strain of S. pneumoniae and monitored over a period of five days for signs of meningitis. Meningitis was confirmed by clinical outcome in the animals, histological investigation of brains, as well as by pleocytosis and presence of bacteria in cerebrospinal fluid (CSF). By inoculation of varying numbers of bacteria (between 1 × 10(4) and 1 × 10(9) CFU/ml in 10 μl), a threshold model was established. The attack rate, pattern and onset of meningitis depended on number of inoculated bacteria. An increased meningitis rate in different experimental groups shows that greater bacterial burden leads to an increased attack rate after intratympanal inoculation. The established animal model provides a potential tool to assess the meningitis risk after cochlear implantation. Its implementation in future studies will allow the investigation of existing and newly developed prostheses for postoperatively infection risk. 相似文献
995.
Arlt MJ Walters DK Banke IJ Steinmann P Puskas GJ Bertz J Rentsch KM Ehrensperger F Born W Fuchs B 《International journal of cancer. Journal international du cancer》2012,131(5):E804-E812
Osteosarcoma (OS) is the most frequent primary bone tumor. Despite multiagent neoadjuvant chemotherapy, patients with metastatic disease have a poor prognosis. Moreover, currently used chemotherapeutics have severe toxic side effects. Thus, novel agents with improved antimetastatic activity and reduced toxicity are needed. Taurolidine, a broad-spectrum antimicrobial, has recently been shown to have antineoplastic properties against a variety of tumors and low systemic toxicity. Consequently, we investigated in our study the antineoplastic potential of taurolidine against OS in two different mouse models. Although both OS cell lines, K7M2 and LM8, were sensitive for the compound in vitro, intraperitoneal application of taurolidine failed to inhibit primary tumor growth. Moreover, it enhanced the metastatic load in both models 1.7- to 20-fold and caused severe liver deformations and up to 40% mortality. Thus, systemic toxicity was further investigated in tumor-free mice histologically, by electron microscopy and by measurements of representative liver enzymes. Taurolidine dose-dependent fibrous thickening of the liver capsule and adhesions and atrophies of the liver lobes were comparable in healthy and tumor-bearing mice. Liver toxicity was further indicated by up to eightfold elevated levels of the liver enzymes alanine transaminase, aspartate transaminase and GLDH in the circulation. Ultrastructural analysis of affected liver tissue showed swollen mitochondria with cristolysis and numerous lipid vacuoles in the cytoplasm of hepatocytes. The findings of our study question the applicability of taurolidine for OS treatment and may suggest the need for caution regarding the widespread clinical use of taurolidine as an antineoplastic agent. 相似文献
996.
Hertwig F Meyer K Braun S Ek S Spang R Pfenninger CV Artner I Prost G Chen X Biegel JA Judkins AR Englund E Nuber UA 《Cancer research》2012,72(13):3381-3392
Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. 相似文献
997.
998.
T Chen L Jansen A Gondos K Emrich B Holleczek S Luttmann A Waldmann H Brenner;THE GEKID CANCER SURVIVAL WORKING GROUP* 《Acta oncologica (Stockholm, Sweden)》2012,51(7):915-921
Abstract Purpose. Population-based studies on cervical cancer providing survival estimates by age, histology, and stage have been sparse. We aimed to derive most up-to-date and detailed survival estimates for cervical cancer patients in Germany. Methods. We used a pooled German national dataset including data from 11 cancer registries covering a population of 33 million people. Included were 15 685 patients diagnosed with cervical cancer from 1997 to 2006. Period analysis was performed to calculate the five-year relative survival (RS) 2002-2006. Trends in survival between 2002 and 2006 were examined using model-based period analysis. Age-adjustment was done using five age groups (15-44, 45-54, 55-64, 65-74, and 75 + years). Results. Overall, age-adjusted five-year relative survival in 2002-2006 was 64.7%. A strong age gradient was observed, with five-year RS decreasing from 81.7% in age group 15-49 years to 46.3% in age group 70 + years. Prognosis furthermore strongly varied by stage, with age-adjusted five-year RS reaching 84.6% for localized, 48.2% for regional, and 17.9% for distant stage. From 2002 to 2006, a significant improvement (4.7 percent units) in overall age-adjusted five-year RS was seen. The improvement was most pronounced for age groups 55-64 years (from 54.2 to 65.6%) and 65-74 years (from 50.0 to 58.1%). Conclusion. In this first comprehensive population-based study from Germany, prognosis of cervical cancer strongly varied by age and stage. Prognosis continued to improve, in particular in age range 55-74 years, in the five-year period assessed. 相似文献
999.
1000.
Katharina Bluemlein Matthias Glückmann Nana-Maria Grüning René Feichtinger Antje Krüger Mirjam Wamelink Hans Lehrach Stephen Tate Daniel Neureiter Barbara Kofler Markus Ralser 《Oncotarget》2012,3(11):1356-1369
The glycolytic enzyme pyruvate kinase (PK) is required for cancer development, and has been implicated in the metabolic transition from oxidative to fermentative metabolism, the Warburg effect. However, the global metabolic response that follows changes in PK activity is not yet fully understood. Using shotgun proteomics, we identified 31 yeast proteins that were regulated in a PK-dependent manner. Selective reaction monitoring confirmed that their expression was dependent on PK isoform, level and activity. Most of the PK targets were amino acid metabolizing enzymes or factors of protein translation, indicating that PK plays a global regulatory role in biosynthethic amino acid metabolism. Indeed, we found strongly altered amino acid profiles when PK levels were changed. Low PK levels increased the cellular glutamine and glutamate concentrations, but decreased the levels of seven amino acids including serine and histidine. To test for evolutionary conservation of this PK function, we quantified orthologues of the identified PK targets in thyroid follicular adenoma, a tumor characterized by high PK levels and low respiratory activity. Aminopeptidase AAP-1 and serine hydroxymethyltransferase SHMT1 both showed PKM2- concentration dependence, and were upregulated in the tumor. Thus, PK expression levels and activity were important for maintaining cellular amino acid homeostasis. Mediating between energy production, ROS clearance and amino acid biosynthesis, PK thus plays a central regulatory role in the metabolism of proliferating cells. 相似文献