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991.
The global cellular response to UV-induced DNA damage has been analyzed in the p53-proficient human lymphoblastoid strain TK6 versus two isogenic derivatives wherein p53 activity was abrogated by diverse experimental approaches: (i) NH32, carrying a homozygous genetic knockout of p53; and (ii) TK6-5E, expressing the human papillomavirus E6 oncoprotein which binds and functionally inactivates p53 protein. Although widely employed as such, the extent to which intracellular E6 expression faithfully models the p53 deficient state still remains uncertain. Following irradiation with UV (either monochromatic 254 nm UV or broad-spectrum simulated sunlight), relative to wild-type TK6, p53-null NH32 exhibited virtually identical clonogenic survival and kinetics of G1-S progression but was nonetheless profoundly resistant to apoptosis. In addition, there were significant qualitative and quantitative differences between NH32 and TK6 with respect to UV mutagenesis at the endogenous hypoxanthine phosphoribosyltransferase (hprt) locus. However, important disparities were observed between genetically p53-deficient NH32 and E6-expressing TK6-5E regarding the manner in which they responded to UV-induced genotoxic stress in relation to wild-type TK6. Indeed, although NH32 and TK6-5E behaved similarly with respect to UV mutagenesis at the hprt locus, there were significant differences between these strains in clonogenic survival, apoptosis, and G1-S progression. Using a well-defined isogenic system, our data clearly reveal the influence of p53 inactivation on the global response of human cells to UV-induced DNA damage, and highlight an important caveat in the field of p53 biology by directly demonstrating that this influence varies substantially depending upon whether p53 function is abrogated genetically, or through E6 oncoprotein expression. 相似文献
992.
993.
This study evaluated the prevalence, risk factors and morbidity associated with specific phobia of illness. Subjects were from a random, community telephone survey of 500 persons age 40 to 65 who lived in Johnson County, Iowa, USA. Forty-three subjects reported that illness fears substantially bothered them personally or affected their medical care, work, or social life. Twenty-one of these subjects could be contacted and agreed to a semistructured interview designed to diagnose specific phobia of illness and screen for other common psychiatric disorders. Based on the interview, 10 subjects met the criteria for specific phobia of illness, 10 for major depressive disorder, 5 for obsessive-compulsive disorder, 5 for generalized anxiety disorder, 4 for hypochondriasis, 4 for panic disorder and 4 for specific phobia other than illness. Assuming subjects not interviewed were similar to subjects who were, the community prevalence of specific phobia of illness is 4.0%. Among the 10 subjects with specific phobia of illness, 7 had prior negative experiences with illness and 8 had comorbid Axis I disorders. The phobia interfered with medical care as well as social functioning for many subjects. These results suggest a prevalence rate and risk factors that will be useful for additional studies of illness phobia. 相似文献
994.
Two strains of transgenic (Tg) mice (Valpha2.3/Vbeta8.2 and Valpha4/Vbeta8.2) have T cell receptors (TCR) that recognize the NAc1-11 immunodominant epitope of the myelin basic protein (MBP). Spontaneous experimental autoimmune encephalomyelitis (sEAE) readily develops in Valpha2.3/Vbeta8.2 mice. T cells in Valpha2.3/Vbeta8.2 mice demonstrate increased levels of CD69, CD44(high) and decreased CD45RB relative to Valpha4/Vbeta8.2 mice. Increased proliferative responses to MBP and high levels of TNF-alpha are seen in Valpha2.3/Vbeta8.2 mice. High IL-4 and TGF-beta production is observed in Valpha4/Vbeta8.2 mice. CC chemokines (macrophage inflammatory protein-1 alpha (MIP-1alpha), RANTES and monocyte chemotactic protein 1 (MCP-1)) are increased in the central nervous system (CNS) of Valpha2.3/Vbeta8.2 mice. Thus, activated Th1 cells in the periphery of Valpha2.3/Vbeta8.2 mice may traffic to the CNS in response to CC chemokines, influencing sEAE. 相似文献
995.
Two-hundred-and-eight acne vulgaris patients were enrolled in a 24-week study to determine the bacterial resistance issues associated with the use of a topical 2% erythromycin gel. It consisted of a 12-week randomized, double-blind, parallel-group treatment phase comparing the active gel versus its vehicle followed by a 12-week single-blind regression phase with gel vehicle only. Bacteriological samples were taken from the face, back and nares for quantification by species and antibiotic resistance characteristics. Acne efficacy was assessed through week 12. The prevalence of erythromycin-resistant coagulase-negative Staphylococci on the face was extremely high (87%) at baseline, increased to 98% by week 12 in the erythromycin-treated group and did not change during regression. The density of these resistant organisms also significantly increased with erythromycin treatment with no change during regression. Similar prevalence and density patterns were also observed on the untreated back and in the nares. Nearly all of the resistant isolates were highly resistant (minimal inhibitory concentrations > 128 microg/ml). Resistance development was confined to the macrolide class of antibiotics. No anti-acne efficacy was observed. 相似文献
996.
Assfalg M Bertini I Bruschi M Michel C Turano P 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(15):9750-9754
The redox reaction between CrO(4)(2-) and the fully reduced three-heme cytochrome c(7) from Desulfuromonas acetoxidans to give chromium(III) and the fully oxidized protein has been followed by NMR spectroscopy. The hyperfine coupling between the oxidized protein protons and chromium(III), which remains bound to the protein, gives rise to line-broadening effects on the NMR resonances that can be transformed into proton-metal distance restraints. Structure calculations based on these unconventional constraints allowed us to demonstrate that chromium(III) binds at a unique site and to locate it on the protein surface. The metal ion is located 7.9 +/- 0.4 A from the iron of heme IV, 16.3 +/- 0.7 A from the iron of heme III, and 22.5 +/- 0.5 A from the iron of heme I. Shift changes caused by the presence of unreactive MoO(4)(2-), a CrO(4)(2-) analogue, indicate the involvement of the same protein area in the anion binding. The titration of the oxidation of cytochrome c(7) shows a detailed mechanism of action. The presence of a specific binding site supports the hypothesis of the biological role of this cytochrome as a metal reductase. 相似文献
997.
Full—length core sequence dependent complex—type glycosylation of hepatitis C virus E2 glycoprotein 总被引:6,自引:0,他引:6
Zhu LX Liu J Li YC Kong YY Staib C Sutter G Wang Y Li GD 《World journal of gastroenterology : WJG》2002,8(3):499-504
AIM:To study HCV polyprotein processing is important for the understanding of the natural history of HCV and the design of vaccines against HCV.The purpose of this study is to investigate the affection of context sequences on hepatitis C virus(HCV) E2 processing.METHODS:HCV genes of different lengths were expressed and compared in vaccinia virus/T7 system with homologous patient serum S94 and mouse anti-serum ME2116 raised against E.coli-derived E2 peptide,respectively Deglycosylation analysis and GNA(Galanthus nivalus)lectin binding assay were performed to study the posttranslational processing of the expressed products.RESULTS:E2 glycoproteins with different molecular weights (-75kDa and -60kDa)were detected using S94 and ME2116,respectively.Deglycosylation analysis showed that this difference was mainly due to different glycosylation.Endo H resistance and its failure to bind to GNA lectin demonstrated that the higher molecular weight form(75kDa)of E2 was complex-type glycosylated,which was readily recognized by homologous patient serum S94.Expression of complex-type glycosylated E2 could not be detected in all of the coretruncated constructs tested,but readily detected in constructs encoding full-length core sequences.CONCLUSION:The upstream conserved full-length core coding sequence was required for the production of E2 glycoproteins carrying complex-type N-glycans which reacted strongly with homologous patient serum and therefore possibly reprsented more mature forms of E2.As complex-type N-glycans indicated modification by Golgi enzymes,the results suggest that the presence of full-length core might be critical for E1/E2 complex to leave ER.Our data may contribute to a better understanding of the processing of HCV structural proteins as well as HCV morphogenesis. 相似文献
998.
Socin HV Born J Wallemacq C Betea D Legros JJ Beckers A 《Clinical neurology and neurosurgery》2002,104(4):367-370
Colloid cysts of the third ventricle are rare, benign cysts of endodermal origin. Between 1989 and 1999, eight patients with this lesion (five females, three males), with a mean age of 40.5 years (range 20–54), were identified out of 1354 operated for tumours of the central nervous system. Among the eight, two were familial. They were half sisters 38 and 28 years-old, who were diagnosed to have colloid cysts of the third ventricle on CT scanning. Transcortical excision yielded 10 and 15 mm sized colloid cysts, respectively. Moreover, both sisters developed a multinodular goiter associated with these congenital tumours. The second sibling developed hyperprolactinemia associated with macroprolactinemia. Pregnancy was only possible after bromocriptine treatment. These cases provide further evidences that colloid cysts probably have an autosomic recessive pattern of inheritance with variable penetrance. 相似文献
999.
1000.