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41.
Paulsson AK McMullen KP Peiffer AM Hinson WH Kearns WT Johnson AJ Lesser GJ Ellis TL Tatter SB Debinski W Shaw EG Chan MD 《中国神经肿瘤杂志》2013,(1):52-52
PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM. 相似文献
42.
Inhibitory synaptogenesis in mouse somatosensory cortex 总被引:4,自引:3,他引:1
It is widely believed that inhibitory synapses are not present or present
in only small numbers in the rodent cerebral cortex during the early
postnatal period when the cortex is being innervated by thalamocortical
fibers. Quantitative electron microscopy was carried out on the
posteromedial barrel subfield of mouse somatosensory cortex from postnatal
day 4 (P4) when thalamocortical innervation of the barrels is becoming
established, through to sexual maturity (>P32), and in adulthood. Both
asymmetrical (putatively excitatory) and symmetrical (putatively
inhibitory) synapses were present in all layers from P4. The symmetrical
synapses were immunoreactive for GABA at all ages. There was a progressive
increase in both asymmetrical and symmetrical synapses up to P32, density
in all layers increasing 16-fold, with the production of asymmetrical
synapses leading and greatly outstripping that of symmetrical. From P32 to
P120, the oldest age studied, synaptic numbers declined by 18% to 13 times
the P4 level, but this affected predominantly layers II/III, IV and V, and
mainly involved asymmetrical synapses. The relative percentage of
asymmetrical to symmetrical synapses from P4 to P8 was 57%/43% but at P32
it was 89.5%/10.5% and in adulthood 85.4%/14.6%. These data indicate that
inhibitory synaptogenesis in the rodent cortex begins earlier than
previously thought, a basis for inhibition being present from the earliest
period. Pruning of all synapses occurs well after thalamocortical
innervation is established and inhibitory synapses are less affected by the
pruning process.
相似文献
43.
The question of payment to egg donors has recently focused the attention of
both the Human Fertilisation and Embryology Authority (HFEA) and licensed
clinics. An acute shortage of egg donors and the rising costs of assisted
conception treatment are matters of grave concern to many patients. To
understand the emotional and social effects of egg sharing and egg
donation, we conducted a survey of attitudes in a group of women who had
some knowledge or experience of egg donation. A total of 750 questionnaires
were sent out of which 217 were returned within the specified time limit.
From these, 107 respondents had experience of egg donation and 110 had made
enquiries about donation. The data from these questionnaires were collated
and tabulated by the National Opinion Polls (NOP) Research Group. An
analysis of the data produced the following key findings: (i) donating or
sharing eggs is a social issue, 94% discuss it with
partners/family/friends; (ii) altruistic motives are not the prerogative of
non-patient volunteers-egg share donors felt that helping the childless was
as important as having a chance of in-vitro fertilization (IVF) for
themselves; (iii) the treatment procedure causes the most anxiety for egg
donors. The recipients were most concerned about delays, donor
characteristics and how the eggs were allocated; (iv) most respondents
(65%) with prior experience of egg sharing would do it again - 63% of egg
share donors, 72% of egg share recipients; (v) cash rewards to egg donors
and outright advertising for donors were rejected by 64 and 62% of the
sample respectively; and (vi) counselling was highly valued and there were
no instances of 'shattered lives' after treatment. The findings do not
support the recently announced intentions of the HFEA to disallow payment
to gamete donors on the grounds of devalued consent. There is no precedent
in modern medicine for egg sharing. The patients surveyed drew a clear
distinction between egg sharing and financial rewards. As long as egg
donation is not covered by the National Health Service, it is fairer to
offer egg sharing than to refuse treatment to those unable to pay.
相似文献
44.
In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable. 相似文献
45.
Carmona-Bayonas A; Soler IO; Gomez FI; Billalabeitia EG; Saura HP; Tafalla MSA; Diaz MP 《Annals of oncology》2007,18(7):1281
Mitotane is often considered the front-line hormonal therapyof adrenocortical carcinoma (ACC). An illustrative case concerningthis issue and the rationale to ponder other alternatives isreported. A 69 year-old woman, diagnosed with ACC was admittedwith hypertensive crisis, supraventricular tachycardia, congestiveheart-failure, diarrhoea and rabdomyolisis. Two years earlier,she had undergone 相似文献
46.
47.
Mariswamy Yamunadevi Edward Gnaraj Wesely M Johnson 《Asian Pacific Journal of Tropical Biomedicine》2011,1(6):428-433
Objective
To determine the chemical profile and steroids composition of the medicinally important plant Aerva lanata (A. lanata) L.Methods
Preliminary phytochemical screening was done by the method as Harborne described. HPTLC studies were carried out as Harborne and Wagner et al described. The Ethyl acetate-ethanol-water (8: 2: 1.2) was employed as mobile phase for glycosides.Results
The desired aim was achieved using Chloroform-acetone (8: 2) as the mobile phase. The methanolic extract of stem, leaves, root, flower and seeds of A. lanata showed the presence of 30 different types of steroids with 30 different Rf values from 0.04 to 0.97. Maximum number (11) of steroids has been observed in leaves followed by root (10).Conclusions
HPTLC profile of steroids has been chosen here to reveal the diversity existing in A. lanata. Such finger printing is useful in differentiating the species from the adulterant and act as biochemical markers for this medicinally important plant in the pharma industry and plant systematic studies. 相似文献48.
Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients 总被引:3,自引:1,他引:3
Nieken J; Mulder NH; Buter J; Vellenga E; Limburg PC; Piers DA; de Vries EG 《Blood》1995,86(3):900-905
Initial studies have shown that recombinant human interleukin-6 (rhIL- 6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II study. rhIL-6 was administered subcutaneously at 150 micrograms once daily for 6 consecutive weeks. Various hematologic and biochemical parameters were measured weekly during rhIL-6 treatment and 4 weeks after rhIL-6 discontinuation. To determine plasma volume and red blood cell (RBC) volume, radioisotope dilution assays with labeled autologous RBCs and with human serum albumin were performed before rhIL-6 administration and on day 8 of rhIL-6 therapy. Hemoglobin levels decreased (mean change +/- SE) 7% +/- 1.5% within 3 days after the start of rhIL-6 therapy (P < .0001) and 19% +/- 2% at week 4. Levels had normalized at follow-up. The plasma volume increased 18% +/- 5% during the first week of rhIL-6 administration (P < .003), whereas RBC volume remained unaffected. The mean RBC corpuscular volume remained unchanged for 2 weeks and then began to decrease slowly, reaching its nadir at week 6 (5% +/- 1%; P < .01). Serum iron levels decreased 65% +/- 12% at week 4 (P < .002) and then returned to initial baseline values. Erythropoietin levels increased rapidly up to 68% at week 3 (P < .0001) and had normalized 4 weeks after rhIL-6 therapy. Levels of serum albumin, prealbumin, and transferrin decreased (P < .0001, P < .003, and P < .0001, respectively), whereas levels of serum amyloid A (P < .003), C-reactive protein, haptoglobin, and alpha-1-antitrypsin (P < .0001) increased during rhIL-6 treatment. All levels returned to pretreatment values after discontinuation of rhIL-6. No alterations in reticulocyte counts, serum lactic dehydrogenase levels, and bilirubin levels were observed. A 6-week regimen of subcutaneous rhIL-6 results in a rapid dilution anemia, caused by an acute and significant increase in plasma volume and followed by hypoferremia. This anemia is reversible after the cessation of rhIL-6 treatment. 相似文献
49.
Fibrinolytic activity was found to be associated with sonicated platelet membranes after separation from cytosol by differential centrifugation. This fibrinolytic activity was attributed to the presence of a plasminogen activator, which was immunochemically identified as urinary-type plasminogen activator (uPA) by antibody neutralization assay, immunoblotting, and immunofluorescence. The molecular weight (mol wt) of this uPA was 54,000 and was present as the single chain form, although a small amount was detected in a higher mol wt complex indicative of a uPA-inhibitor complex. Treatment of membrane preparations with Triton X-100, 3 mol/L KCl, and 0.1 mol/L glycine, (pH 2.3), but not 10 mmol/L ethylenediamine tetraacetic acid (EDTA), removed the uPA from the membrane. This suggests that uPA is a peripheral membrane protein and that metal ions do not mediate protein- membrane association. Immunofluorescent staining revealed the presence of uPA on the outer surface of the platelet in preparations of intact unstimulated platelets. Thus, uPA is associated with the outer leaflet of the platelet membrane and may be involved with the acceleration of thrombus degradation observed with platelet-rich thrombi. 相似文献
50.
Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome 总被引:8,自引:4,他引:8
Peters C; Balthazor M; Shapiro EG; King RJ; Kollman C; Hegland JD; Henslee- Downey J; Trigg ME; Cowan MJ; Sanders J; Bunin N; Weinstein H; Lenarsky C; Falk P; Harris R; Bowen T; Williams TE; Grayson GH; Warkentin P; Sender L; Cool VA; Crittenden M; Packman S; Kaplan P; Lockman LA 《Blood》1996,87(11):4894-4902
Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bons marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population. 相似文献