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991.
A review of the diagnosis and management of male breast cancer 总被引:8,自引:0,他引:8
Giordano SH 《The oncologist》2005,10(7):471-479
Male breast cancer is an uncommon disease although the incidence has increased over the past 25 years. As with many other rare "orphan" diseases, male breast cancer is understudied. The rarity of the disease precludes prospective randomized clinical trials. In addition, few researchers and minimal funding have focused on breast cancer in men, but further work is clearly needed to better understand this disease. It shares many similarities with breast cancer in women; yet some clear differences have emerged. In this article, the latest information on the epidemiology, biology, and treatment of male breast cancer is reviewed. 相似文献
992.
BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ 总被引:12,自引:0,他引:12
Litman R Peng M Jin Z Zhang F Zhang J Powell S Andreassen PR Cantor SB 《Cancer cell》2005,8(3):255-265
We showed in this study that cells deficient of the BRCA1-associated BACH1 helicase, also known as BRIP1, failed to elicit homologous recombination (HR) after DNA double-stranded breaks (DSBs). BACH1-deficient cells were also sensitive to mitomycin C (MMC) and underwent MMC-induced chromosome instability. Moreover, we identified a homozygous nonsense mutation in BACH1 in a FA-J patient-derived cell line and could not detect BACH1 protein in this cell line. Expression of wild-type BACH1 in this cell line reduced the accumulation of cells at G2/M phases following exposure to DNA crosslinkers, a characteristic of Fanconi anemia (FA) cells. These results support the conclusion that BACH1 is FANCJ. 相似文献
993.
Forastiere AA Ang K Brizel D Brockstein BE Dunphy F Eisele DW Goepfert H Hicks WL Kies MS Lydiatt WM Maghami E McCaffrey T Mittal BB Pfister DG Pinto HA Posner MR Ridge JA Samant S Schuller DE Shah JP Spencer S Trotti A Wheeler RH Wolf GT Worden F Yueh B;National Comprehensive Cancer Network 《Journal of the National Comprehensive Cancer Network : JNCCN》2005,3(3):316-391
994.
Tinkelman D Nordyke RJ Isonaka S George D DesFosses K Nonikov D 《Journal of managed care pharmacy : JMCP》2005,11(1):25-32
OBJECTIVES: Chronic obstructive pulmonary disease (COPD) as a cause of disability with subsequent costs remains poorly recognized. The small, growing body of literature on COPD shows that it is one of the leading causes of missed work.greater than asthma or diabetes. However, much less is known about the impact of COPD on long-term disability (LTD). Because the health care burden for disabled, working-age patients will fall heavily on managed care organizations, better estimates of the economic and pharmacoeconomic costs of COPD are required. We seek to improve understanding of the burden of COPD on several national LTD programs. METHODS: We reviewed occupational health and disability literature and government statistics to determine how long-term, respiratory-related disability is addressed by disability pension programs in 8 developed countries (Canada, France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States). We then applied respiratory-specific disability definitions to country-specific population and pension information to estimate the potential burden of COPD on LTD insurance programs in each country. RESULTS: Comprehensive, relevant data to evaluate respiratory-related disability are lacking. Of the study countries, only the United States has explicit respiratory specific criteria for disability eligibility, which are based solely on spirometry. We estimate that the total burden of COPD in the study countries may range from 5 billion dollars to as high as 25 billion dollars per year if all persons who met U.S. eligibility criteria for respiratory-related disability were granted compensation. CONCLUSION: The potential burden of COPD on LTD programs may be large. The lack of standard criteria for respiratory-related disability may lead to underrecognition of COPD's true potential impact. Further work is needed to develop consistent and cost-effective ways to measure the impact of COPD and to assist in disability determination for COPD patients. 相似文献
995.
KTX 0101 is the sodium salt of the physiological ketone, D-beta-hydroxybutyrate (betaOHB). This neuroprotectant, which has recently successfully completed clinical Phase IA evaluation, is being developed as an intravenous infusion fluid to prevent the cognitive deficits caused by ischemic foci in the brain during cardiopulmonary bypass (CPB) surgery. KTX 0101 maintains cellular viability under conditions of physiological stress by acting as a "superfuel" for efficient ATP production in the brain and peripheral tissues. Unlike glucose, this ketone does not require phosphorylation before entering the TCA cycle, thereby sparing vital ATP stores. Although no reliable models of CPB-induced ischemia exist, KTX 0101 is powerfully cytoprotectant under the more severe ischemic conditions of global and focal cerebral ischemia, cardiac ischemia and lung hemorrhage. Neuroprotection has been demonstrated by reductions in infarct volume, edema, markers of apoptosis and functional impairment. One significant difference between KTX 0101 and other potential neuroprotectants in development is that betaOHB is a component of human metabolic physiology which exploits the body's own neuroprotective mechanisms. KTX 0101 also protects hippocampal organotypic cultures against early and delayed cell death in an in vitro model of status epilepticus, indicating that acute KTX 0101 intervention in this condition could help prevent the development of epileptiform foci, a key mechanism in the etiology of intractable epilepsy. In models of chronic neurodegenerative disorders, KTX 0101 protects neurons against damage caused by dopaminergic neurotoxins and by the fragment of beta-amyloid, Abeta(1-42), implying possible therapeutic applications for ketogenic strategies in treating Parkinson's and Alzheimer's diseases. Major obstacles to the use of KTX 0101 for long term therapy in chronic disorders, e.g., Parkinson's and Alzheimer's diseases, are the sodium loading problem and the need to administer it in relatively large amounts because of its rapid mitochondrial metabolism. These issues are being addressed by designing and synthesizing orally bioavailable multimers of betaOHB with improved pharmacokinetics. 相似文献
996.
O'Toole SA Sheppard BL Sheils O O'Leary JJ Spengler B Christoffel V 《Planta medica》2005,71(5):435-439
The aim of this study was to identify genomic aberrations in endometrial cancer cells treated with the phyto-estrogenic compounds tectorigenin, irigenin and apigenin and to compare with those treated with beta-estradiol using array-based comparative genomic hybridisation (array CGH). The microarray contains 287 targets and includes telomeres, microdeletions, oncogenes and tumour suppressor genes and has increased mapping resolution compared to conventional CGH. An endometrial cancer cell line (Ishikawa) was cultured and treated with the phyto-estrogens. Treated cells were examined using the CGH microarray. Over 20 % of the array genes were aberrated in the cells treated with beta-estradiol, tectorigenin and irigenin compared to 3 % in those treated with the same concentration of apigenin. Protein kinase c zeta form, insulin, insulin receptor and protein-tyrosine phosphatase non-receptor-type 1 which are involved in insulin metabolism were aberrated by tectorigenin and irigenin. Apigenin may play a role in the treatment of endometrial cancer and in the treatment of postmenopausal women. Further studies in normal endometrium and primary endometrial cancer cells are needed to elucidate the role of the phyto-estrogens. 相似文献
997.
Lu SX Takach EJ Solomon M Zhu Q Law SJ Hsieh FY 《Journal of pharmaceutical sciences》2005,94(4):788-797
Prostate specific membrane antigen (PSMA) is a well-characterized glycoprotein overexpressed on the surface of prostate cancer cells. The novel radiopharmaceutical 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) radiolabeled with Yttrium (90Y) or Indium (111In) conjugated with anti-PSMA genetically engineered humanized monoclonal antibody (huJ591) has been investigated to target prostate cancer cells. The immunoconjugate of huJ591 with the analog of the cytotoxic drug maytansine, DM1 (N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine) has also been developed at Millennium Pharmaceuticals. Activation of the DOTA molecule, resulting in 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid mono-(N-hydroxysuccinimidyl) ester (DOTA-NHS), allows conjugation with the anti-PSMA antibody through lysine residues in the antibody. The objectives of the study were to characterize the unstable chemical properties of DOTA-NHS before bioconjugation with huJ591, evaluate the binding profiles of DOTA to huJ591, and calculate trace metal elements (which may disturb 90Y or 111In labeling efficacy to the DOTA-huJ591 conjugate). A novel LC/MS/MS (Liquid Chromatography/Mass Spectrometry/Mass Spectrometry) quantitation method was developed to monitor the stability of DOTA-NHS in solid form and its bioconjugation chemistry reactions. Meanwhile, metal analysis was quantified by Inductively Coupled Plasma Mass Spectrometry (ICP/MS) to estimate the amounts of trace metals in DOTA-NHS and ensure radiolabeling efficiency of the conjugate at the radiopharmacy. MALDI-TOF MS (Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry) was used to identify levels of DOTA or DM1conjugation in DOTA-huJ591 and DM1-huJ591 conjugates, respectively. 相似文献
998.
999.
Salminen O Whiteaker P Grady SR Collins AC McIntosh JM Marks MJ 《Neuropharmacology》2005,48(5):696-705
The subunit composition and pharmacology of alpha-Conotoxin MII-binding (alpha-CtxMII) nicotinic acetylcholine receptors (nAChR) was studied by an improved [(125)I]-alpha-CtxMII membrane binding method. This binding method facilitates pharmacological studies that have been difficult to accomplish with [(125)I]-alpha-CtxMII autoradiography or alpha-CtxMII inhibition of [(125)I]-epibatidine binding. Binding densities and K(d)-values obtained by this [(125)I]-alpha-CtxMII membrane binding were similar to the values obtained by autoradiography or alpha-CtxMII inhibition of [(125)I]-epibatidine binding, verifying that each of these approaches measures the same nAChR population. Binding results with nAChR subunit-null mutant mice confirm and extend observations from earlier studies: [(125)I]-alpha-CtxMII binding measures two sets of alpha6beta2* nAChR (alpha4alpha6beta2beta3 or alpha6beta2beta3). Most nicotinic agonists and antagonists show monophasic inhibition of [(125)I]-alpha-CtxMII binding, indicating that alpha4alpha6beta2beta3 and alpha6beta2beta3 have similar binding properties. Comparison of the binding and activation profiles of alpha6beta2* nAChR to those of other nAChR subtypes (alpha4beta2* and beta4*) indicates that these receptors have distinctly different pharmacology indicating that it may be possible to target alpha6beta2* nAChR selectively to develop compounds that might be therapeutically useful. 相似文献
1000.