全文获取类型
收费全文 | 355篇 |
免费 | 21篇 |
国内免费 | 28篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 16篇 |
妇产科学 | 2篇 |
基础医学 | 54篇 |
口腔科学 | 6篇 |
临床医学 | 38篇 |
内科学 | 51篇 |
皮肤病学 | 2篇 |
神经病学 | 9篇 |
特种医学 | 39篇 |
外科学 | 32篇 |
综合类 | 6篇 |
预防医学 | 25篇 |
眼科学 | 90篇 |
药学 | 11篇 |
肿瘤学 | 20篇 |
出版年
2023年 | 4篇 |
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 4篇 |
2018年 | 8篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 5篇 |
2014年 | 9篇 |
2013年 | 11篇 |
2012年 | 21篇 |
2011年 | 18篇 |
2010年 | 11篇 |
2009年 | 14篇 |
2008年 | 13篇 |
2007年 | 37篇 |
2006年 | 19篇 |
2005年 | 20篇 |
2004年 | 8篇 |
2003年 | 14篇 |
2002年 | 12篇 |
2001年 | 15篇 |
2000年 | 17篇 |
1999年 | 6篇 |
1998年 | 14篇 |
1997年 | 10篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1989年 | 7篇 |
1988年 | 7篇 |
1986年 | 2篇 |
1985年 | 6篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 3篇 |
1955年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有404条查询结果,搜索用时 31 毫秒
1.
Prostaglandin F and E levels during endotoxin-induced pulmonary hypertension in calves 总被引:10,自引:0,他引:10
Anderson FL; Tsagaris TJ; Jubiz W; Kuida H 《The American journal of physiology》1975,228(5):1479-1482
2.
Marchant D Gogat K Boutboul S Péquignot M Sternberg C Dureau P Roche O Uteza Y Hache JC Puech B Puech V Dumur V Mouillon M Munier FL Schorderet DF Marsac C Dufier JL Abitbol M 《Human mutation》2001,17(3):235
ABSTRACT We report five novel VMD2 mutations in Best's macular dystrophy patients (S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8. Direct sequencing indicated that these shifts are caused by mono-allelic transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6. Five novel "silent" polymorphisms are also reported: 213T>C, 323C>A, 1514A>G, 1661C>T, and 1712T>C. Hum Mutat 17:235, 2001. 相似文献
3.
Systematic investigation of families of children suffering from retinoblastoma reveals more and more cases of retinoma or phthisis bulbi, cases which used to be called "spontaneous regression". Between 1975 and 1991, we have in this way discovered 11 cases (7%) certain to be carrying retinoma or phthisis bulbi, and a further 5 cases where the same diagnosis is highly probable. Of the 11 certain cases, 5 are unilateral, 6 bilateral, and 8 present family history of the disease. Of the total number of 17 eyes, 16 present retinoma, 1 phthisis bulbi. On clinical examination, all (100%) showed characteristic lesions in the form of greyish homogenous elevated masses in the vitreous cavity. 11 presented calcifications (69%) and in 14 disturbance of the pigment epithelium occurred (87%). The average follow-up is 4 years. Of the 11 patients, 8 are of procreating age and have up to now 25 offsprings. Amongst these, 15 have retinoblastoma (60%), 2 retinoma and phthisis bulbi (8%). All except one of the retinoblastoma cases are bilateral. This study would appear to show that retinoma occurs with a higher frequency than that which is usually given. The figures show clearly that retinoblastoma and retinoma derive from the same genetic disturbances, possibly at different times during cell maturation, and consequently require the same investigation and follow-up. 相似文献
4.
BACKGROUND: Despite an increased awareness among clinicians regarding pain and pain management for infants undergoing surgery, pain associated with procedures performed outside the operating room may not be adequately managed. PURPOSE: To examine the beliefs and self-described behavior of physicians and nurses regarding the management of procedural pain in newborn infants. METHODS: A survey was distributed to 467 clinicians (nurses and physicians) working in 11 level II and 4 level III nurseries in a large metropolitan area. Respondents were asked to rate the painfulness of 12 common bedside nursery procedures and how often pharmacologic and nonpharmacologic (comfort) measures are currently used and should be used for those procedures. Demographic data were also collected. RESULTS: Surveys were completed by 374 clinicians (80% response rate). Physicians and nurses believe infants feel as much pain as adults and that 9 of the 12 listed procedures are moderately to very painful. Neither pharmacologic nor comfort measures are believed to be used frequently, even for the most painful procedures. Physicians and nurses believe both pharmacologic and comfort measures should be used more frequently, but nurses believe comfort measures should be used more frequently than do physicians. Beliefs about infant pain and procedural pain were related to pain management preferences. Physicians' but not nurses' ratings were associated with significant personal pain. CONCLUSIONS: Despite their beliefs that infants experience significant procedure-related pain, clinicians believe pain management for infants remains below optimal levels. Barriers to more consistent and effective pain management need to be identified and surmounted. 相似文献
5.
Abril N; Luque-Romero FL; Prieto-Alamo MJ; Rafferty JA; Margison GP; Pueyo C 《Carcinogenesis》1997,18(10):1883-1888
Here we confirm and extend our previous studies demonstrating that the
mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is
markedly enhanced (not prevented) in bacteria expressing the O6-
alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli
ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt
ATase sensitizes the bacteria to the lethal effects of these carcinogens,
suggesting that one or more of the potentially mutagenic lesions induced by
DBE and DBM in the presence of Ogt has additional lethal capacity. We
further demonstrate that the sensitization to both lethality and
mutagenesis by DBE and DBM is a property shared by other DNA
alkyltransferases. This objective was accomplished by quantifying the
induction of mutations and lethal events in ogt- ada- E. coli expressing an
exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian
recombinant ATases enhanced the lethal and mutagenic actions of DBE and
suppressed the lack of sensitivity of the vector- transformed bacteria to
DBM. In most cases the order of effectiveness of the ATases ranked: murine
> human > Ogt > rat. Further comparisons included the full-length
Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the
O6-methylguanine binding domain of the protein. The full-length Ada ATase
was effective in enhancing the lethality but not the mutagenicity induced
by DBE and DBM. The T-ada ATase provided less sensitization than Ada to
lethality by DBE, but of the three bacterial ATases T-ada yielded the
highest sensitization to mutagenesis by this compound. T-ada and Ada ATases
were in general less effective than the mammalian versions, with the
exception of the rat recombinant ATase. The effectiveness of the different
mammalian and bacterial ATases in promoting the deleterious actions of
dibromoalkanes was compared with the effectiveness of these proteins in
suppressing the lethal and mutagenic effects induced by
N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and
mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase,
since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt-
ada- cells showed no effect, in spite of the reported potential of
bioactive dihaloethane- derived species to alkylate Trx.
相似文献
6.
7.
Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells 总被引:1,自引:0,他引:1
Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out. 相似文献
8.
Early proliferation of CCR5(+) CD38(+++) antigen-specific CD4(+) Th1 effector cells during primary HIV-1 infection 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《Blood》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Zaunders JJ Munier ML Kaufmann DE Ip S Grey P Smith D Ramacciotti T Quan D Finlayson R Kaldor J Rosenberg ES Walker BD Cooper DA Kelleher AD 《Blood》2005,106(5):1660-1667
We investigated whether HIV-1 antigen-specific CD4(+) T cells expressed the viral coreceptor CCR5 during primary HIV-1 infection (PHI). In the peripheral blood of subjects with very early PHI (< 22 days after onset of symptoms), there was a 10- to 20-fold increase in the proportion of highly activated (CD38(+++)) and proliferating (Ki-67(+)) CD4(+) T cells that expressed CCR5(+), and were mostly T-cell intracellular antigen-1 (TIA-1)(+) perforin(+) granzyme B(+). Inthe same patient samples, CD4(+) T cells producing interferon (IFN)-gamma in response to HIV group-specific antigen (Gag) peptides were readily detected (median, 0.58%) by intracellular cytokine assay-these cells were again predominantly CD38(+++), Ki-67(+), and TIA-(++), as well as Bcl-2(low). On average, 20% of the Gag-specific CD4(+) T cells also expressed interleukin-2 (IL-2) and were CD127 (IL-7R)(+). Taken together, these results suggest that Gag-specific T-helper 1 (Th1) effector cells express CCR5 during the primary response and may include precursors of long-term self-renewing memory cells. However, in PHI subjects with later presentation, antigen-specific CD4(+) T cells could not be readily detected (median, 0.08%), coinciding with a 5-fold lower level of the CCR5(+)CD38(+++) CD4(+) T cells. These results suggest that the antiviral response to HIV-1 infection includes highly activated CCR5(+)CD4(+) cytotoxic effector cells, which are susceptible to both apoptosis and cytopathic infection with HIV-1, and rapidly decline. 相似文献
9.
Mineralocorticoid receptor (MR), highly expressed in the hippocampus, binds corticosteroid hormones and coordinately participates, with the glucocorticoid receptor, to the control of stress responses, memorization, and behavior. To investigate the impact of MR in neuronal survival, we generated murine embryonic stem (ES) cells that overexpress human MR (hMR) (P1-hMR) and are induced to differentiate into mature neurons. We showed that recombinant MR expression increased throughout differentiation and is 2-fold higher in P1-hMR ES-derived neurons compared with wild-type controls, whereas glucocorticoid receptor expression was unaffected. Although proliferation and early neuronal differentiation were comparable in P1-hMR and wild-type ES cells, MR overexpression was associated with higher late neuronal marker expression (microtubule-associated protein 2 and β-tubulin III). This was accompanied by a shift towards neuron survival with an increased ratio of anti- vs. proapoptotic molecules and 50% decreased caspase 3 activity. Knocking down MR overexpression by small interfering RNA drastically reversed neuroprotective effects with reduced Bcl(2)/Bax ratio and decreased microtubule-associated protein 2 expression. P1-hMR neurons were protected against oxidative stress-induced apoptosis through reduced caspase 3 activation and drastically increased Bcl(2)/Bax ratio and β-tubulin III expression. We demonstrated the involvement of MR in neuronal differentiation and survival and identify MR as an important neuroprotective mediator opening potential pharmacological strategies. 相似文献