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Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase) 总被引:2,自引:0,他引:2
Bonthron David T.; Brady Nlcola; Donaldson lain A.; Steinmann Beat 《Human molecular genetics》1994,3(9):1627-1631
Essential fructosuria is one of the oldest known inborn errorsof metabolism. It is a benign condition which is believed toresult from deficiency of hepatic fructokinase (ketohexokinase,KHK, E.C.2.7.1.3). This enzyme catalyses the first step of metabolismof dietary fructose, conversion of fructose to fructose-1-phosphate.Despite the early recognition of this disorder, the primarystructure of human KHK and the molecular basis of essentialfructosuria have not been previously defined. In this report,the isolation and sequencing of full-length cDNA clones encodinghuman ketohexokinase are described. Alternative mRNA speciesand alternative KHK isozymes are produced by alternative polyadenylationand splicing of the KHK gene. The KHK proteins show a high levelof sequence conservation relative to rat KHK. Direct evidencethat mutation of the KHK structural gene is the cause of essentialfructosuria was also obtained. In a well-characterized family,in which three of eight siblings have fructosurla, all affectedindividuals are compound heterozygotes for two mutations Gly40Argand Ala43Thr. Both mutations result from G 相似文献
6.
Erkki Lotspeich Markus Schoene Heinz Gerngroß Roland Schmidt Reinhard Steinmann Marco Ramadani Susanne Gansauge 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2007,392(5):559-566
Introduction Postoperative treatment for colorectal cancer depends on tumor stage as defined by the International Union Against Cancer
(UICC). Adjuvant chemotherapy is not recommended in patients without lymph node involvement (UICC stages I and II). As many
as 20–30% of these patients, however, will develop recurrence.
Aims and objectives We conducted this study to determine the presence of disseminated tumor cells in the lymph nodes by quantitative real-time
polymerase chain reaction (QRT-PCR) for cytokeratin 20 (CK20) in an attempt to provide supplementary information compared
to histopathological findings.
Materials and methods Using a standard QRT-PCR assay, we examined primary tumors and 391 lymph nodes from 31 patients with completely resected colorectal
cancer.
Results Of the 31 primary tumors, 29 were positive for CK20 by QRT-PCR.
Discussion An examination of the lymph nodes from the 29 patients with CK20-positive primary tumors revealed that 35 (92.1% sensitivity)
of the 38 histopathologically positive lymph nodes and 54 (16.7%) of the 324 histopathologically negative lymph nodes were
positive by molecular analysis. CK20 expression was detected in 10 (100%) of 10 patients with a histopathologically positive
lymph node status (pN1). In 9 (47.4%) of 19 patients with negative histopathological results (pN0), we detected a CK20 mRNA
signal in at least one lymph node. Whereas eight patients with histopathologically negative lymph nodes could be upstaged
on the basis of the molecular findings, no patient would be downstaged.
Conclusion Our results suggest that QRT-PCR for CK20 is a useful tool for the quantitative detection of micrometastases in the regional
lymph nodes. We introduce a standardized procedure that integrates a molecular diagnostic technique in the clinical staging. 相似文献
7.
CGP 37849 and CGP 39551: novel and potent competitive N-methyl-D-aspartate receptor antagonists with oral activity 总被引:8,自引:3,他引:5 下载免费PDF全文
G E Fagg H R Olpe M F Pozza J Baud M Steinmann M Schmutz C Portet P Baumann K Thedinga H Bittiger 《British journal of pharmacology》1990,99(4):791-797
1. The pharmacological properties of CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid; 4-methyl-APPA) and its carboxyethylester, CGP 39551, novel unsaturated analogues of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoate (AP5), were evaluated in rodent brain in vitro and in vivo. 2. Radioligand binding experiments demonstrated that CGP 37849 potently (Ki 220 nM) and competitively inhibited NMDA-sensitive L-[3H]-glutamate binding to postsynaptic density (PSD) fractions from rat brain. It inhibited the binding of the selective NMDA receptor antagonist, [3H]-((+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), with a Ki of 35 nM, and was 4, 5 and 7 fold more potent than the antagonists [+/-)-cis-4-phosphonomethylpiperidine-2-carboxylic acid) (CGS 19755), CPP and D-AP5, respectively. Inhibitory activity was associated exclusively with the trans configuration of the APPA molecule and with the D-stereoisomer. CGP 39551 showed weaker activity at NMDA receptor recognition sites and both compounds were weak or inactive at 18 other receptor binding sites. 3. CGP 37849 and CGP 39551 were inactive as inhibitors of L-[3H]-glutamate uptake into rat brain synaptosomes and had no effect on the release of endogenous glutamate from rat hippocampal slices evoked by electrical field stimulation. 4. In the hippocampal slice in vitro, CGP 37849 selectively and reversibly antagonized NMDA-evoked increases in CA1 pyramidal cell firing rate.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
Cosma A Bühler S Nagaraj R Staib C Hammarin AL Wahren B Goebel FD Erfle V Sutter G 《Clinical and diagnostic laboratory immunology》2004,11(2):406-410
Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays. Currently, the presence of neutralizing antibodies to vaccinia virus is measured using a plaque reduction neutralization test, but this method is time-consuming and labor-intensive and has a subjective readout. Here, we describe an innovative neutralization assay based on a modified vaccinia virus Ankara (MVA) vector expressing the green fluorescent protein (MVA-gfp). This MVA-gfp neutralization assay is rapid and sensitive and has a high-throughput potential. Thus, it is suitable to monitor the immune response and eventually the efficacy of a large campaign of vaccination against smallpox and to study the vector-specific immune response in clinical trials that use genetically engineered vaccinia viruses. Most importantly, application of the highly attenuated MVA eliminates the safety concern in using the replication-competent vaccinia virus in the standard clinical laboratory. 相似文献
9.
Taillandier A Zurutuza L Muller F Simon-Bouy B Serre JL Bird L Brenner R Boute O Cousin J Gaillard D Heidemann PH Steinmann B Wallot M Mornet E 《Human mutation》1999,13(2):171-172
Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/ bone/kidney tissue alkaline phosphatase (L/B/K ALP) activity. We report the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 9 families affected by severe hypophosphatasia. Fourteen distinct mutations were found, 3 of which were previously reported in the North American or Japanese populations. Seven of the 11 new mutations were missense mutations (M45L, R119H, G145V, C184Y and H154Y, D289V, E459K), the four others were 2 single nucleotide deletions (544delG and 1172delC), a mutation affecting donor splice site (862 + 5A) and a nonsense mutation (R411X). 相似文献
10.
Katrina Mackay Michael Raghunath rea Superti-Furga Beat Steinmann Raymond Dalgleish 《Clinical genetics》1996,49(6):286-295
Three patients with Ehlers-Danlos syndrome type IV (EDS IV) and biochemical evidence of structural defects in collagen III were investigated for mutations within the collagen III gene ( COL3A1 ). Single strand conformation polymorphism analysis of α1(III) cDNA indicated the presence of different heterozygous sequence changes in each of the patients. Nucleotide sequencing revealed mutations leading to the substitution of glycine 400 with glutamic acid, glycine 595 with cysteine, and glycine 1003 with aspartic acid. EDS IV is a life-threatening disorder which, as the clinical histories of our patients and their families show, still often escapes diagnosis. Biochemical and molecular studies can clarify the diagnosis and help provide appropriate management and counselling. 相似文献