全文获取类型
收费全文 | 688篇 |
免费 | 56篇 |
国内免费 | 1篇 |
专业分类
儿科学 | 53篇 |
妇产科学 | 10篇 |
基础医学 | 83篇 |
口腔科学 | 13篇 |
临床医学 | 65篇 |
内科学 | 134篇 |
皮肤病学 | 10篇 |
神经病学 | 9篇 |
特种医学 | 152篇 |
外科学 | 65篇 |
综合类 | 8篇 |
预防医学 | 27篇 |
眼科学 | 3篇 |
药学 | 28篇 |
中国医学 | 1篇 |
肿瘤学 | 84篇 |
出版年
2021年 | 2篇 |
2020年 | 3篇 |
2018年 | 7篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 11篇 |
2013年 | 21篇 |
2012年 | 13篇 |
2011年 | 13篇 |
2010年 | 28篇 |
2009年 | 20篇 |
2008年 | 16篇 |
2007年 | 10篇 |
2006年 | 17篇 |
2005年 | 28篇 |
2004年 | 21篇 |
2003年 | 22篇 |
2002年 | 13篇 |
2001年 | 19篇 |
2000年 | 17篇 |
1999年 | 17篇 |
1998年 | 33篇 |
1997年 | 30篇 |
1996年 | 30篇 |
1995年 | 28篇 |
1994年 | 32篇 |
1993年 | 21篇 |
1992年 | 15篇 |
1991年 | 16篇 |
1990年 | 15篇 |
1989年 | 20篇 |
1988年 | 21篇 |
1987年 | 16篇 |
1986年 | 13篇 |
1985年 | 19篇 |
1984年 | 11篇 |
1983年 | 14篇 |
1982年 | 23篇 |
1981年 | 18篇 |
1980年 | 11篇 |
1979年 | 3篇 |
1978年 | 5篇 |
1977年 | 8篇 |
1976年 | 16篇 |
1975年 | 9篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1968年 | 2篇 |
1936年 | 1篇 |
排序方式: 共有745条查询结果,搜索用时 0 毫秒
1.
2.
Steenbergen EJ; Verhagen OJ; van Leeuwen EF; van den Berg H; von dem Borne AE; van der Schoot CE 《Blood》1995,86(2):692-702
Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL. 相似文献
3.
4.
AIM: To determine the prevalence of Chlamydia pneumoniae DNA in infrequently examined blood vessels. METHODS: Vessels obtained from 15 men and six women at coronary artery bypass surgery were tested by a nested polymerase chain reaction (PCR) assay for C pneumoniae DNA. RESULTS: Chlamydia pneumoniae DNA was detected in four of six atheromatous ascending aorta specimens but in none of eight non-atheromatous aorta specimens, in six of 11 atheromatous internal mammary artery specimens but in none of seven non-atheromatous internal mammary artery specimens, in five of seven long saphenous vein specimens showing evidence of disease but in none of 12 specimens without evidence of disease, and in two of three previously grafted veins. Overall, C pneumoniae occurred significantly more often in diseased than in normal vessels (p = < 0.00001). CONCLUSIONS: Chlamydia pneumoniae is often present in diseased areas of arteries, including the internal mammary arteries, and even in diseased areas of veins. It is not present in apparently healthy areas of either type of vessel. 相似文献
5.
Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains 总被引:6,自引:2,他引:6
Flint J; Bates GP; Clark K; Dorman A; Willingham D; Roe BA; Micklem G; Higgs DR; Louis EJ 《Human molecular genetics》1997,6(8):1305-1313
We have sequenced and compared DNA from the ends of three human
chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are
subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub-
domains with entirely different patterns of homology to other chromosome
ends. The distal regions contain numerous, short (<2 kb) segments of
interrupted homology to many other human telomeric regions. The proximal
regions show much longer (approximately 10-40 kb) uninterrupted homology to
a few chromosome ends. A comparison of all yeast subtelomeric regions
indicates that they too are subdivided by degenerate TTAGGG repeats into
distal and proximal sub-domains with similarly different patterns of
identity to other non-homologous chromosome ends. Sequence comparisons
indicate that the distal and proximal sub-domains do not interact with each
other and that they interact quite differently with the corresponding
regions on other, non- homologous, chromosomes. These findings suggest that
the degenerate TTAGGG repeats identify a previously unrecognized,
evolutionarily conserved boundary between remarkably different subtelomeric
domains.
相似文献
6.
Casey Graham; Plummer Sarah; Hoeltge Gerald; Scanlon David; Fasching Clare; Stanbridge Eric J. 《Human molecular genetics》1993,2(11):1921-1927
Rearrangements or deletions of chromosome 17 are the most frequentlyobserved genetic changes identified in breast tumors. Molecularanalyses suggest that in addition to the p53 gene on 17p13.1there may be at least three other tumor suppressor genes onchromosome 17 involved in breast cancer. Regions of loss ofheterozygosity (LOH) identified on 17p13.3 and 17q12-qter occurfrequently in breast tumors, and the BRCA-1 gene has been mappedto 17q21 by genetic linkage analysis. Here we provide biologicalevidence for the presence of a growth suppressor gene(s) onchromosome 17 that results In the In vitro growth suppressionof the p53 wild-type MCF 7 breast cancer cell line. We haveIntroduced a normal chromosome 17 into MCF 7 cells by microcellmediatedchromosome transfer (MMCT), and demonstrate that cells growtharrest before 10 to 12 population doublings. In contrast, theintroduction of a normal chromosome 13 had no effect upon growthof these cells either In vitro or In vivo. These data providedirect functional evidence for the presence of a growth suppressorgene(s) on chromosome 17, which is not p53, and which may representone of several gene(s) that play a critical role in the developmentof breast cancer. 相似文献
7.
Ko JM Yau WL Chan PL Lung HL Yang L Lo PH Tang JC Srivastava G Stanbridge EJ Lung ML 《Genes, chromosomes & cancer》2005,43(3):284-293
Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an approximately 2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer. 相似文献
8.
Canfield MC; Tamarappoo BK; Moses AM; Verkman AS; Holtzman EJ 《Human molecular genetics》1997,6(11):1865-1871
Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused
most often by mutations in the vasopressin V2 receptor (AVPR2). We studied
a family which included a female patient with NDI with symptoms dating from
infancy. The patient responded to large doses of desmopressin (dDAVP) which
decreased urine volume from 10 to 4 I/day. Neither the parents nor the
three sisters were polyuric. The patient was found to be a compound
heterozygote for two novel recessive point mutations in the aquaporin-2
(AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is
the site for inhibition of water permeation by mercurial compounds and is
located near to the NPA motif conserved in all aquaporins. Osmotic water
permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2
was not increased over water control, while expression of L22V cRNA
increased the Pf to approximately 60% of that for wild-type AQP2.
Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the
function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO
cells showed that the C181W mutant had an endoplasmic reticulum-like
intracellular distribution, whereas L22V and wild-type AQP2 showed endosome
and plasma membrane staining. Water permeability assays showed a high Pf in
cells expressing wild-type and L22V AQP2. This study indicates that AQP2
mutations can confer partially responsive NDI.
相似文献
9.
Russell EJ; Geremia GK; Johnson CE; Huckman MS; Ramsey RG; Washburn-Bleck J; Turner DA; Norusis M 《Radiology》1987,165(3):609-617
Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes. 相似文献
10.
Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols 总被引:47,自引:7,他引:47
In order to study the biological activities of tea preparations and
purified tea polyphenols, their growth inhibitory effects were investigated
using four human cancer cell lines. Growth inhibition was measured by
[3H]thymidine incorporation after 48 h of treatment. The green tea
catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)- epigallocatechin
(EGC) displayed strong growth inhibitory effects against lung tumor cell
lines H661 and H1299, with estimated IC50 values of 22 microM, but were
less effective against lung cancer cell line H441 and colon cancer cell
line HT-29 with IC50 values 2- to 3- fold higher.
(-)-Epicatechin-3-gallate, had lower activities, and (-)- epicatechin was
even less effective. Preparations of green tea polyphenols and theaflavins
had higher activities than extracts of green tea and decaffeinated green
tea. The results suggest that the growth inhibitory activity of tea
extracts is caused by the activities of different tea polyphenols. Exposure
of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the
induction of apoptosis as determined by an annexin V apoptosis assay,
showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM
of these compounds, the apoptosis indices were 82, 76 and 78%,
respectively. Incubation of H661 cells with EGCG also induced a
dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused
apoptosis in a manner similar to that caused by EGCG. The EGCG-induced
apoptosis in H661 cells was completely inhibited by exogenously added
catalase (50 units/ml). These results suggest that tea polyphenol-induced
production of H2O2 may mediate apoptosis and that this may contribute to
the growth inhibitory activities of tea polyphenols in vitro.
相似文献