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Gianetti E Hall JE Au MG Kaiser UB Quinton R Stewart JA Metzger DL Pitteloud N Mericq V Merino PM Levitsky LL Izatt L Lang-Muritano M Fujimoto VY Dluhy RG Chase ML Crowley WF Plummer L Seminara SB 《The Journal of clinical endocrinology and metabolism》2012,97(9):E1798-E1807
Context: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. Objective: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. Subjects: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. Results: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. Conclusions: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes. 相似文献
83.
AF Chase DZ Chase CT Fisher SJ Leisz JF Weishampel 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(32):12916-12921
The application of light detection and ranging (LiDAR), a laser-based remote-sensing technology that is capable of penetrating overlying vegetation and forest canopies, is generating a fundamental shift in Mesoamerican archaeology and has the potential to transform research in forested areas world-wide. Much as radiocarbon dating that half a century ago moved archaeology forward by grounding archaeological remains in time, LiDAR is proving to be a catalyst for an improved spatial understanding of the past. With LiDAR, ancient societies can be contextualized within a fully defined landscape. Interpretations about the scale and organization of densely forested sites no longer are constrained by sample size, as they were when mapping required laborious on-ground survey. The ability to articulate ancient landscapes fully permits a better understanding of the complexity of ancient Mesoamerican urbanism and also aids in modern conservation efforts. The importance of this geospatial innovation is demonstrated with newly acquired LiDAR data from the archaeological sites of Caracol, Cayo, Belize and Angamuco, Michoacán, Mexico. These data illustrate the potential of technology to act as a catalytic enabler of rapid transformational change in archaeological research and interpretation and also underscore the value of on-the-ground archaeological investigation in validating and contextualizing results. 相似文献
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Score J Hidalgo-Curtis C Jones AV Winkelmann N Skinner A Ward D Zoi K Ernst T Stegelmann F Döhner K Chase A Cross NC 《Blood》2012,119(5):1208-1213
The polycomb repressive complex 2 (PRC2) is a highly conserved histone H3 lysine 27 methyltransferase that regulates the expression of developmental genes. Inactivating mutations of the catalytic component of PRC2, EZH2, are seen in myeloid disorders. We reasoned that the other 2 core PRC2 components, SUZ12 and EED, may also be mutational targets in these diseases, as well as associated factors such as JARID2. SUZ12 mutations were identified in 1 of 2 patients with myelodysplastic syndrome/myeloproliferative neoplasms with 17q acquired uniparental disomy and in 2 of 2 myelofibrosis cases with focal 17q11 deletions. All 3 were missense mutations affecting the highly conserved VEFS domain. Analysis of a further 146 myelodysplastic syndrome/myeloproliferative neoplasm patients revealed an additional VEFS domain mutant, yielding a total mutation frequency of 1.4% (2 of 148). We did not find mutations of JARID2 or EED in association with acquired uniparental disomy for chromosome 6p or 11q, respectively; however, screening unselected cases identified missense mutations in EED (1 of 148; 1%) and JARID2 (3 of 148; 2%). All 3 SUZ12 mutations tested and the EED mutation reduced PRC2 histone methyltransferase activity in vitro, demonstrating that PRC2 function may be compromised in myeloid disorders by mutation of distinct genes. 相似文献
86.
目的:总结以病人为中心的口腔科门诊数字化建设的经验。方法:从诊疗手段、就医流程、医疗文书以及科室管理4个方面总结广州军区武汉总医院口腔科门诊数字化建设的概况。结果:2009年以来开始进行El腔科门诊的数字化建设,经过3年多的运行,科室工作流程优化明显,提高了工作效率和医疗服务质量。结论:科室的数字化建设有助于提高科室的工作效率和医疗服务质量,充分体现了”以病人为中心”这一理念。 相似文献
87.
Ford C Yusim K Ioerger T Feng S Chase M Greene M Korber B Fortune S 《Tuberculosis (Edinburgh, Scotland)》2012,92(3):194-201
The emergence of whole genome sequencing (WGS) technologies as primary research tools has allowed for the detection of genetic diversity in Mycobacterium tuberculosis (Mtb) with unprecedented resolution. WGS has been used to address a broad range of topics, including the dynamics of evolution, transmission and treatment. Here, we have analyzed 55 publically available genomes to reconstruct the phylogeny of Mtb, and we have addressed complications that arise during the analysis of publically available WGS data. Additionally, we have reviewed the application of WGS to the study of Mtb and discuss those areas still to be addressed, moving from global (phylogeography), to local (transmission chains and circulating strain diversity), to the single patient (clonal heterogeneity) and to the bacterium itself (evolutionary studies). Finally, we discuss the current WGS approaches, their strengths and limitations. 相似文献
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The ventrolateral subdivision of the periaqueductal gray (vlPAG) and the adjacent dorsal mesencephalic reticular formation (dMRF) are involved in the modulation of active (rapid eye movement) sleep (AS). In order to determine the effects on AS of the suppression of neuronal activity in these regions, muscimol, a GABA receptor A (GABA(A)) receptor agonist, and bicuculline, a GABA(A) receptor antagonist, were microinjected bilaterally in guinea pigs and the states of sleep and wakefulness were examined. The main effect of muscimol was an increase in AS; this increase occurred in conjunction with a reduction in the time spent in wakefulness. The powerful effect of muscimol was striking especially when considering the small amount of naturally-occurring AS that is present in this species. Additional observable effects that were induced by muscimol were: 1) long lasting episodes of hypotonia/atonia during wakefulness and quiet sleep that included a lack of extensor tone in the hind limbs, and 2) frequently occurring cortical spindles, similar to those observed during naturally-occurring quiet sleep (sleep spindles), that were present during wakefulness. Conversely, bilateral microinjections of bicuculline induced a prolonged state of wakefulness and blocked the effect of subsequent injections of muscimol. These data suggest that endogenous GABA acts on GABA(A) receptors within the vlPAG and dMRF to promote AS in the guinea pig. 相似文献