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951.
Mutational analysis of NOTCH1, 2, 3 and 4 genes in common solid cancers and acute leukemias 总被引:2,自引:0,他引:2
Lee SH Jeong EG Yoo NJ Lee SH 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2007,115(12):1357-1363
NOTCH proteins (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) play crucial roles in embryonic development. Also, mounting evidence indicates that NOTCH contributes to the pathogenesis of hematopoietic and solid malignancies. Recent studies reported a high incidence of gain-of-function mutations of the NOTCH1 gene in T-cell acute lymphoblastic leukemias (ALL). To see whether NOTCH1 mutation occurs in other malignancies, we analyzed NOTCH1 for the detection of somatic mutations in 334 malignancies, including 48 lung, 48 breast, 48 colorectal and 48 gastric carcinomas, and 142 acute leukemias (105 acute myelogenous leukemias, 32 B-ALLs and 4 T-ALLs) by single-strand conformation polymorphism assay. Also, to see whether other NOTCH genes harbor somatic mutations, we analyzed NOTCH2, NOTCH3 and NOTCH4 genes in the same tissue samples. Overall, we detected three NOTCH mutations in the cancers, which consisted of one NOTCH1 mutation in the T-ALLs (25.0%), one NOTCH2 mutation in the breast carcinomas (2.1%), and one NOTCH3 mutation in the colorectal carcinomas (2.0%). There was no NOTCH mutation in other malignancies analyzed. Our data indicate that NOTCH1 is mutated in T-ALL, but not in other common human cancers, and that NOTCH2, NOTCH3 and NOTH4 genes are rarely mutated in common human cancers. Despite the importance of NOTCH activation in many types of human cancers, mutation of NOTCH genes, except for NOTCH1 mutation in T-ALL, may not play an important role in the tumorigenesis of common cancers. 相似文献
952.
Jeong EG Lee SH Lee HW Soung YH Yoo NJ Lee SH 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2007,115(8):900-905
FLASH was initially identified as a pro-apoptotic protein that transmits an apoptosis signal during death receptor-induced apoptosis. Additionally, diverse biologic roles of FLASH, including TNF-induced NF-kappaB activation, cell-cycle progression and cell division, have been identified. Although such functions are important in cancer pathogenesis, little is known about the alterations of FLASH gene and FLASH protein expression in human cancers. In this study, we analyzed the expression of FLASH protein in 60 gastric adenocarcinomas by immunohistochemistry. We furthermore analyzed mutation of FLASH in exon 8, where two polyadenine tracts ((A)8 and (A)9) are present, by single-strand conformation polymorphism (SSCP) assay in 184 gastric adenocarcinomas. By immunohistochemistry, FLASH protein expression in cancer cells was detected positively in 42 gastric carcinoma tissues (70%), whereas its expression in epithelial cells of normal gastric mucosa was shown as no or very weak intensity. Mutational analysis detected one FLASH mutation in the gastric carcinomas (0.5%). The increased expression of FLASH in the malignant gastric epithelial cells compared to the normal mucosal epithelial cells suggests that FLASH expression may play a role in gastric tumorigenesis. Also, the data suggest that somatic mutation of FLASH is a rare event in gastric carcinomas. 相似文献
953.
Kim SJ Song CH Sung HJ Yoo YD Geum DH Park SH Yoo JH Oh JH Shin HJ Kim SH Kim JS Kim BS 《Stem cells and development》2007,16(3):421-428
Co-culture of human embryonic stem (ES) cells on mouse fibroblast feeders is the commonly used method for in vitro expansion of human ES cells in an undifferentiated state. However, it has potential risks of pathogen transmission from animals; thus, human cell-derived feeders have been employed to minimize this problem. In this study, we compared human placenta-derived feeders with bone marrow to demonstrate its effectiveness as feeders for in vitro long-term culture of human ES cells. We cultured a human ES cell line, SNUhES3, on human placenta-derived mesenchymal stem cell feeders and compared their culture efficiency with human bone marrow-derived feeders and control group (mouse fibroblast feeders, STO). The mean number of human ES cell colonies was 166 +/- 35 in the placenta feeders; this was significantly higher than bone marrow-derived feeders (87 +/- 16, p < 0.05). We could propagate the culture of SNUhES3 on the placenta feeders past the 50th week similar to control group. During the culture, the maintenance of undifferentiated state of SNUhES3 was demonstrated by the expression of SSEA-4, TRA-1-81, TRA-1-60, and Oct-4. However, we failed to propagate the culture of human ES cells on the human bone marrow-derived feeders past the 5th week. The efficiency of embryoid body formation was similar between placenta and control group, indicating the preservation of differentiation ability. Thus, placenta-derived feeders are more efficient for the long-term in vitro culture of human ES cells than bone marrow-derived feeders suggesting the possible role of placenta as a source for human cell-derived feeders. 相似文献
954.
Mussel adhesive proteins (MAPs) have received increased attention as potential environmentally friendly adhesives under aqueous conditions and in medicine. However, attempts to produce functional recombinant MAPs (mainly foot protein type 1, fp-1) by several expression systems have failed. Even though we previously reported a functional expression of recombinant foot protein type 5 (fp-5) with significant adhesive ability in Escherichia coli, its practical use was limited by several problems such as low production yield, low purification yield, and high levels of post-purification insolubility. Here, to overcome these limitations, we designed and constructed the novel type of hybrid mussel bioadhesive fp-151, a fusion protein comprising six fp-1 decapeptide repeats at each fp-5 terminus. Using micro- and bulk-scale characterization and mammalian cell-adhesion analyses, we demonstrate that fp-151 has the potential to be a practical bioadhesive with strong adhesive ability, a simple purification process ( approximately 1g-purified protein per 1l-pilot-scale fed-batch bioreactor culture), proper manipulation properties ( approximately 330g/l solubility), and high biocompatibility. 相似文献
955.
Cho PY Kim TI Yoo WG Li S Hong SJ Kim TY Park YS Song KY Choi MH Hong ST Chung YJ LoVerde PT Osman A 《Parasitology research》2007,102(1):53-56
WD40-repeat proteins have four to eight repeating units flanked by Gly-His (GH) and Trp-Asp (WD) at both termini and folds
into a β-propeller. A polypeptide deduced from a Clonorchis sinensis cDNA clone analyzed to have seven WD40-repeats and predicted to form a β-propeller (CsWD1). The CsWD1 protein was expressed
stage-specifically in the metacercariae and localized in the tegumental syncytium. The CsWD1 protein is suggested to serve
as a platform for interacting partner proteins in the tegumental syncytium of C. sinensis metacercariae. 相似文献
956.
Bi W Yan J Shi X Yuva-Paylor LA Antalffy BA Goldman A Yoo JW Noebels JL Armstrong DL Paylor R Lupski JR 《Human molecular genetics》2007,16(15):1802-1813
Smith-Magenis syndrome (SMS) is associated with an approximately 3.7 Mb common deletion in 17p11.2 and characterized by its craniofacial and neurobehavioral abnormalities. The reciprocal duplication leads to dup(17)(p11.2p11.2) associated with the Potocki-Lupski syndrome (PLS), a neurological disorder whose features include autism. Retinoic acid induced 1 (RAI1) appears to be responsible for the majority of clinical features in both SMS and PLS. Mouse models of these syndromes harboring an approximately 2 Mb chromosome engineered deletion and duplication, respectively, displayed abnormal locomotor activity and/or learning deficits. To determine the contribution of RAI1 in the neurobehavioral traits in SMS, we performed a battery of behavioral tests on Rai1 mutant mice and the Df(11)17-1/+ mice that have a small deletion of approximately 590 kb. The mice with the small deletion were hypoactive like the large deletion mice and they also showed learning deficits. The Rai1+/- mice exhibited normal locomotor activity. However, they had an abnormal electroencephalogram with overt seizure observed in a subset of mice. The few surviving Rai1-/- mice displayed more severe neurobehavioral abnormalities including hind limb clasping, overt seizures, motor impairment and context- and tone-dependant learning deficits. X-gal staining of the Rai1+/- mice suggests that Rai1 is predominantly expressed in neurons of the hippocampus and the cerebellum. Our results suggest that Rai1 is a critical gene in the central nervous system functioning in a dosage sensitive manner and that the neurobehavioral phenotype is modified by regulator(s) in the approximately 590 kb genomic interval, wherein the major modifier affecting the craniofacial penetrance resides. 相似文献
957.
Age, sex, and comorbidities were considered in comparing reference data for health-related quality of life in the general and cancer populations 总被引:2,自引:0,他引:2
OBJECTIVES: The purpose of this study was to provide reference data for health-related quality of life (HRQOL) in the general Korean population so that the data could be compared with those of cancer patients. Reference data enable more detailed insights into treatments for and care of cancer patients. STUDY DESIGN AND SETTING: We constructed a questionnaire that included the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30, LC13, STO22, and BR23, the Hospital Anxiety and Depression Scale, and the McGill Quality-of-Life questionnaire and administered a population-based, cross-sectional survey to 1,000 persons. RESULTS: Men reported better functioning and existential well-being, but women reported more physical symptoms, anxiety, and depression. Most scores of functioning and well-being scales decreased and most physical symptoms, anxiety, and depression increased with increasing age. Increasing the number of comorbidities had a negative effect on all functions and most symptom scales. CONCLUSION: Our findings suggest that age, sex, and comorbidities must always be considered when comparing HRQOL data from the general population with those from cancer patients. 相似文献
958.
Young Hun Kim Minsung Kim Ji Eun Kim Miyoun Yoo Heung Kyoung Lee Chong Ock Lee Minjin Yoo Kwan-Young Jung Yeongrin Kim Sang Un Choi Chi Hoon Park 《Oncology Letters》2021,21(6)
Since bromodomain containing 4 (brd4) has been considered as a prominent cancer target, numerous attempts have been made to develop potent brd4 bromodomain inhibitors. The present study provided a novel chemical scaffold which inhibited brd4 activity. Mid-throughput screening against brd4 bromodomain was performed using alpha-screen and homogeneous time-resolved fluorescence assays. Furthermore, cell cytotoxicity and xenograft assays were performed to examine if the compound was effective both in vitro and in vivo. As a result, it was revealed that compounds having naphthalene-1,4-dione scaffold inhibited the binding of bromodomain to acetylated histone. The compounds with naphthalene-1,4-dione had cytotoxic effects against the Ty82 cell line, a NUT midline carcinoma cell line, whose proliferation is dependent on brd4 activity. A10, one of the compounds with naphthalene-1,4-dione scaffold, also exhibited tumor growth inhibition effects in the xenograft assay. In addition, the compounds exhibited cytotoxic effects against gastric cancer cell lines which were resistant to I-BET-762, a BET bromodomain inhibitor. In conclusion, the novel scaffold to suppress brd4 activity was effective against cancer cells both in vitro and in vivo. 相似文献
959.
Kim SJ Park HB Lee JS Jo NH Yoo KH Baek D Kang BW Cho JH Oh CH 《European journal of medicinal chemistry》2007,42(9):1176-1183
The synthesis of a new series of 1beta-methylcarbapenems having cyclic sulfonamide moieties is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituent on the pyrrolidine ring was investigated. A particular compound (IIIi) having 2-methyl-[1,2,6]thiadiazinan-1,1-dioxide moiety showed the most potent antibacterial activity. 相似文献
960.
Data required for the determination of the absolute air kerma rate for (60)Co and (137)Cs gamma-rays using spherical cavity chambers were calculated using the EGS4 Monte Carlo system. Mass energy-absorption coefficient ratio and the stopping power ratio were calculated for a 10 cm(3) primary standard graphite-walled ionization chamber from the unfolded energy pulse height distributions of (60)Co and (137)Cs sources. Wall correction factors and non-uniformity correction factors for two graphite and one air equivalent plastic walled ionization chambers were also calculated with EGS4 code. The wall correction factors were compared with those determined by an experimental extrapolation method. To check the accuracy of the calculations the results were compared with those obtained from other primary standard laboratories such as NIST and NRCC. For a 10 cm(3) graphite ionization chamber, the mass energy-absorption coefficient ratios were 0.99917 for (60)Co and 1.0004 for (137)Cs. The values differed by 0.02-0.05 % for (60)Co and 0.11 % for (137)Cs from those of two laboratories. The stopping power ratios were 0.99984 for (60)Co and 1.0087 for (137)Cs. Comparison with NIST values showed differences of 0.06 % for (60)Co and 0.04 % for (137)Cs. The wall correction factors were obtained and they were different by 0.6-1.1 % for (60)Co and (137)Cs compared to the experimental linear extrapolation method. These values were compared with Monte Carlo derived values from other laboratories. The non-uniformity correction factors were also calculated and they differed from unity, the traditional value used in most standard national metrology laboratories. 相似文献