全文获取类型
收费全文 | 26099篇 |
免费 | 2042篇 |
国内免费 | 100篇 |
专业分类
耳鼻咽喉 | 245篇 |
儿科学 | 783篇 |
妇产科学 | 534篇 |
基础医学 | 3393篇 |
口腔科学 | 345篇 |
临床医学 | 3287篇 |
内科学 | 5849篇 |
皮肤病学 | 357篇 |
神经病学 | 2028篇 |
特种医学 | 820篇 |
外科学 | 3520篇 |
综合类 | 378篇 |
一般理论 | 31篇 |
预防医学 | 2345篇 |
眼科学 | 868篇 |
药学 | 1697篇 |
中国医学 | 61篇 |
肿瘤学 | 1700篇 |
出版年
2023年 | 180篇 |
2022年 | 237篇 |
2021年 | 496篇 |
2020年 | 360篇 |
2019年 | 621篇 |
2018年 | 654篇 |
2017年 | 521篇 |
2016年 | 539篇 |
2015年 | 586篇 |
2014年 | 856篇 |
2013年 | 1230篇 |
2012年 | 1729篇 |
2011年 | 1685篇 |
2010年 | 997篇 |
2009年 | 931篇 |
2008年 | 1563篇 |
2007年 | 1669篇 |
2006年 | 1637篇 |
2005年 | 1599篇 |
2004年 | 1529篇 |
2003年 | 1455篇 |
2002年 | 1288篇 |
2001年 | 361篇 |
2000年 | 327篇 |
1999年 | 302篇 |
1998年 | 280篇 |
1997年 | 242篇 |
1996年 | 197篇 |
1995年 | 235篇 |
1994年 | 192篇 |
1993年 | 166篇 |
1992年 | 222篇 |
1991年 | 181篇 |
1990年 | 181篇 |
1989年 | 167篇 |
1988年 | 184篇 |
1987年 | 168篇 |
1986年 | 151篇 |
1985年 | 130篇 |
1984年 | 141篇 |
1983年 | 142篇 |
1982年 | 145篇 |
1981年 | 127篇 |
1980年 | 122篇 |
1979年 | 101篇 |
1978年 | 105篇 |
1977年 | 113篇 |
1976年 | 83篇 |
1975年 | 61篇 |
1974年 | 71篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
91.
New evidence for a gating action of norepinephrine in central neuronal circuits of mammalian brain 总被引:3,自引:0,他引:3
Barry D. Waterhouse Francis M. Sessler Cheng Jung-Tung Donald J. Woodward S.Ausim Azizi Hylan C. Moises 《Brain research bulletin》1988,21(3):425-432
Many previous studies have examined the effects of norepinephrine (NE) on neuronal responsiveness to synaptic inputs and putative transmitter substances and have described differential depressant actions of NE on stimulus evoked versus spontaneous discharge such that the "signal to noise" ratio of threshold responses was increased. In the present studies, similar experimental strategies employing a combination of microiontophoresis, single unit recording and afferent pathway stimulation in intact anesthetized and brain tissue slice preparations have revealed noradrenergic "gating" actions whereby weak or subthreshold synaptic stimuli can evoke threshold neuronal responses in the presence of iontophoretically applied NE or following electrical stimulation of the locus coeruleus. Overall, these results suggest that potentially threshold excitatory and inhibitory synaptic inputs may normally arrive at central neurons but appear weak or absent except during behavioral conditions favoring the synaptic release of NE. As such, these findings provide evidence that signal to noise ratio may not be the only potential modulatory action expressed by NE in noradrenergic target circuits of the mammalian brain. 相似文献
92.
Structure-activity relationships for epidermal ornithine decarboxylase induction and skin tumor promotion by anthrones 总被引:2,自引:0,他引:2
DiGiovanni John; Kruszewski Francis H.; Coombs Maurice M.; Bhatt Tarlochan S.; Pezeshk Abbas 《Carcinogenesis》1988,9(8):1437-1443
The present study was designed to compare the skin tumor promotingand epidermal ornithine decarboxylase (ODC) inducing activitiesof various structural analogs of anthralin (1, 8-dihydroxy-9-anthrone)and chrysarobin (1, 8-dihydroxy-3- methyl-9-anthrone). Groupsof 30 SENCAR mice each were initiated with 7, 12-dimethylbenz[a]anthraceneand 2 weeks later promoted with once- or twice-weekly applicationsof various doses of these anthrone derivatives. Carbon-10 (C10)-acylderivatives of anthralin were active skin tumor promoters inthe range of 25440 nmol per mouse. 10-Acetylanthralinwas significantly more active than 10-myristoyl-anthralin atlow doses (e.g. 25 and 50 nmol per mouse) and nearly as potentas the unsubstituted compound. Higher doses ( 100 nmol per mouse)of this derivative were toxic, hence, reducing the final papillomaresponse. On a relative activity scale where anthralin is 1.0,these derivatives had activities that were 0.7 and 0.2, respectively.10, 10-Dipropylanthralin was totally inactive at the doses tested.C6-Substituted derivatives of chrysarobin demonstrated diversetumor promoting activities when tested in the range of 25440nmol per mouse. On a relative activity scale where chrysarobinis 1.0, 6-methoxychrysarobin (physcion anthrone) was 0.9, whereas6-hydroxychrysarobin (emodin anthrone) had no activity. Chrysophanicacid (1, 8-dihydroxy-3-methyl-9, 10-anthraquinone) was alsoinactive as a tumor promoter at the doses tested. In general,the tumor promoting activities of these anthrone derivativescorrelated very well with their ability to induce epidermalODC after a single topical application indicating an importantrole for this enzyme in skin tumor promotion by anthones. Theability of C10-substituted derivatives of anthralin to undergobase catalyzed oxidation in vitro correlated with both ODC inducingand tumor promoting activities. In addition, copper(II) bis(diisopropylsalicylate)was found to inhibit both ODC induction and skin tumor promotionby chrysarobin. These latter data, when taken together, suggesta role for oxidation at C10 in skin tumor promotion by anthronederivatives. 相似文献
93.
Seasonal prevalence of major congenital malformations in the Fylde of Lancashire 1957-1981. 总被引:2,自引:2,他引:0 下载免费PDF全文
The seasonal prevalence of major congenital malformations was studied in a prospective survey of 88,449 children born in the circumscribed Fylde of Lancashire to residents there over 25 years. Ascertainment was thought to be as complete as was practically possible because cases were recorded daily by one, and for 17 years the only, paediatrician and a very high rate of necropsies was maintained. The number of malformations were classified by month of maternal last menstrual period and seasonal variation was assessed by three statistical models. Neural tube defects showed a significant seasonal variation in month of last menstrual period but not in month of birth. From May 1956 to April 1968, when the prevalence of neural tube defects was high (5.5 per 1000 total births), conceptions were significantly more common in December to May. For anencephaly alone the figures were not significant, but spina bifida and cranium bifidum were more common in March to May. From May 1968 to April 1981, when the prevalence of neural tube defects fell below the national average, the significant variations disappeared. Seasonality for spina bifida and cranium bifidum was seen only in "singles" (cases with no other major lesion), but for anencephaly it was seen only in "multiples" (cases with other lesions). The three types of cardiac septal defect and persistent ductus each showed a higher prevalence of conceptions at some time during May to October. In contrast the commonest group of cyanotic cases showed no such pattern but with greater numbers in winter. There was evidence of a seasonal variation for bilateral renal agenesis and for vesicoureteric reflux as ascertained. Seasonal prevalence in an aetiological factor for certain malformations of the central nervous system, cardiac and urinary systems. 相似文献
94.
95.
We investigated 10 unrelated Chinese patients with type 2 Gaucher disease and performed ex vivo expression for the novel mutations to characterize their functional defects. These patients were diagnosed by enzymatic assays and clinicopathologic features over the past five years in a national centre in China. Genomic DNA was sequenced by a two-stage PCR approach for mutations in the functional GBA gene. Novel mutations were expressed with baculovirus-transfected Sf21 cells. Six novel mutations were found (in traditional nomenclature): P122L, Y363C, N382K, L383R, L385P, and M416V. Review of reported mutations indicated clustering of type 2 mutations in three regions of the GBA gene. Expression of novel mutations revealed that the enzyme defect could arise from one of two mechanisms: loss of catalytic activity (Y363C and M416V) or enzyme instability (P122L and N382K). 相似文献
96.
Chen D Ueda R Harding F Patil N Mao Y Kurahara C Platenburg G Huang M 《European journal of immunology》2003,33(1):172-182
Linkage studies indicate close associations of certain HLA alleles with autoimmune diseases. To better understand how specific HLA alleles are related to disease pathogenesis, we have generated an HLA DR3/DQ2 transgenic mouse utilizing a 550-kb yeast artificial chromosome (YAC) construct containing the complete DRalpha, DRbeta1, DRbeta3, DQalpha, and DQbeta regions. The transgenic mouse (4D1/C2D) in an I-Abeta(o) background appears healthy with no signs of autoimmune diseases. Lymphoid tissues as well as CD4(+) T cells develop normally. Characterization of the transgene expression demonstrates that approximately 90% of B cells express high levels of DR3 and 50-70% of B cells express DQ2. CD11c(+) dendritic cells express high levels of DR and DQ. Approximately 12-18% of resting T cells are positive for DR expression, and further up-regulation to 40-50% expression is seen upon activation with anti-CD3/anti-CD28 mAb. These results suggest that the transgenic construct confers a high fidelity to the normal human temporal and spatial expression profile. Analysis of T cell receptor repertoire in transgenic mice confirms that DR3/DQ2 are able to mediate thymic selection. Furthermore, transgenic mice respond to a DR3-restricted antigen, demonstrating antigen processing and presentation by antigen-presenting cells (APC). Purified T cells from ovalbumin (OVA)-immunized 4D1 mice respond to human APC co-cultured with OVA, suggesting appropriate antigen/DR3 or DQ2 recognition by murine T cells. Immunoglobulin isotype switching is also observed, indicating functional T-B cognate interactions. Thus, the DR3/DQ2 transgenic mouse has normal lymphoid development and functionality that are mediated by HLA transgenes and can be used to investigate HLA-associated immunological questions. 相似文献
97.
Emanuel Dean A.; Scott Jerry B.; Haddy Francis J. 《The American journal of physiology》1959,197(3):637-642
98.
Martineau M Jalali GR Barber KE Broadfield ZJ Cheung KL Lilleyman J Moorman AV Richards S Robinson HM Ross F Harrison CJ 《Genes, chromosomes & cancer》2005,43(1):54-71
This study was undertaken in order to compare the interphase and metaphase cytogenetics of 28 patients with ETV6/RUNX1 positive acute lymphoblastic leukemia, at diagnosis and relapse. The median time to relapse was 26 months. The significant fusion positive population heterogeneity revealed at interphase by a commercial probe for ETV6/RUNX1 fusion has not been described before. Six diagnostic samples had a single abnormal population; others had up to five each, which differed in the numbers of RUNX1 signals, and in the retention or loss of the second ETV6 signal. In contrast, the number of fusion signals was more constant. At relapse, there were fewer populations; the largest or unique clone was sometimes a re-emergence of a minor, diagnostic one, with a retained copy of ETV6 and the most RUNX1 signals. Abnormal, fusion negative clones were identified in bone marrow samples at extra-medullary relapse. Variant three or four-way translocations, which involved chromosomes 12 and 21, were prominent among the complex rearrangements revealed by metaphase FISH. The frequency of their occurrence at diagnosis and reappearance at relapse, sometimes accompanied by minor clonal evolution, was another new observation. Other recurrent cytogenetic features included a second copy of the fusion signal in six cases, partial duplication of the long arm of the X chromosome in two cases, and trisomy 10 in three cases. In comparing our data with previously reported cases, a picture is beginning to emerge of certain diagnostic features, which may provide circumstantial evidence of an increased risk of relapse. 相似文献
99.
Fiona Campbell MD MRCPath John M Geraghty MBBS MRCPath Mark A.C Appleton MBChB MRCPath E.Dillwyn Williams MD FRCP FRCPath Geraint T Williams MD FRCP FRCPath 《Human pathology》1998,29(12):1531-1535
Colorectal tumorigenesis in familial adenomatous polyposis (FAP) results from somatic mutation of either the normal APC allele or another growth control gene in epithelial cells bearing a germline APC defect. The rate at which tumors develop is therefore dependent on the somatic mutation frequency; it is not known whether this is normal or elevated in FAP. We aimed to quantify stem cell somatic mutation in FAP, comparing it with hereditary nonpolyposis colorectal cancer (HNPCC) and Crohn's disease (CD). Stem cell somatic mutation frequency was studied in 47 FAP patients, 5 HNPCC patients, and 13 CD patients, all younger than 49 years, by quantifying crypt-restricted loss of O-acetyltransferase activity in sections of morphologically normal colonic mucosa from individuals heterozygous for this monogenically inherited polymorphism. Median stem cell somatic mutation frequency was significantly higher in FAP than HNPCC (4.2 × 10−4v 1.4 × 10−4, Mann-Whitney U, P < .02). The level in CD (4.0 × 10−4) was similar to FAR Mutated crypts occurred in groups more frequently in FAP (22%) than HNPCC (12%) or CD (10%), suggesting an increase in stem cell division associated with crypt fission in FAP. We conclude that stem cell somatic mutation frequency is raised in non-neoplastic colorectal mucosa in FAR This is probably related to increased stem cell proliferation and contributes to the high rate of tumor formation in this condition. 相似文献
100.
The atheroprotective effect of 17beta-estradiol depends on complex interactions in adaptive immunity 下载免费PDF全文
Elhage R Gourdy P Jawien J Brouchet L Castano C Fievet C Hansson GK Arnal JF Bayard F 《The American journal of pathology》2005,167(1):267-274
Estradiol prevents fatty streak formation in chow-fed atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice. We previously reported that fatty streak development of immunodeficient ApoE(-/-)/recombination activating gene 2 (RAG-2(-/-)) double-deficient mice was insensitive to estradiol. In the present work, we demonstrate that the reconstitution of ApoE(-/-)/RAG-2(-/-) with bone marrow from immunocompetent ApoE(-/-)/RAG-2(+/+) mice restores the protective effect of estradiol on fatty streak constitution. We extended this demonstration to the model of low-density lipoprotein receptor-deficient mice, establishing the obligatory role of mature lymphocytes in this process. We then investigated whether the protective effect of estradiol was mediated by a specific lymphocyte subpopulation by studying the hormonal effect on fatty streak constitution in recently developed models of ApoE(-/-) mice deficient in selective T-lymphocyte subsets (either TCRalphabeta+, CD4+, CD8+, or TCRgammadelta+ lymphocytes) or B lymphocytes. In all these specifically immunodeficient mice, estradiol administration to ovariectomized mice conferred protection as in immunocompetent ApoE(-/-) mice, clearly demonstrating that no single lymphocyte subpopulation was specifically required for this effect. These results point to additional lymphocyte-dependent mechanisms such as modulating the interactions among lymphocytes and between lymphocytes and endothelial and/or antigen-presenting cells. 相似文献