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41.
Ingrid V. Allen 《Immunology》1965,8(5):475-483
The effect of total body irradiation on the development of delayed hypersensitivity and on the febrile response to specific antigen has been studied in guinea-pigs with the following results:
1. 200 R. whole body irradiation in guinea-pigs, while suppressing circulating antibody response, did not prevent the development of delayed hypersensitivity.
2. Irradiated and non-irradiated hypersensitive animals had an equal febrile response to systemic challenge with specific antigen.
3. Serum from antigen-challenged, irradiated, hypersensitive animals contained a pyrogenic factor of the endogenous serum type capable of producing fever in normal recipients.
These results support the conclusion that production of circulating specific antibody is not essential either for development of delayed hypersensitivity or for the febrile response of the hypersensitive animal to specific antigen.
相似文献42.
Studies on the mechanism of phorbol ester-induced inhibition of intercellular junctional communication 总被引:1,自引:0,他引:1
Intercellular gap-junctional communication was measured using[14C]citrulline incorporation in co-cultures of argininosuccinatelyase-deficient human fibroblasts and argininosuccinate synthetase-deficientChinese Hamster V79 cells. As previously shown, in this systemjunctional communication is completely inhibited by the tumorpromoting phorbol ester 12-O-tetra-decanoylphorbol-13-acetate(TPA). In the absence of extracellular calcium, TPA inhibitionwas less pronounced. However, synergism with calcium ionophoreA23187 could not be demonstrated. Chlorpromazine, trifluoperazineand 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl esterpartially antagonised the effect of TPA. No antagonism was demonstrablebetween calmidazolium and TPA. Treatment of co-cultures withexogenous phospholipase C or 1-oleoyl-2-acetylglycerol (OAG)resulted in communication inhibition, suggesting that proteinkinase C activation is involved in the mechanism of phorbolester-mediated communication inhibition. However co-cultureswhich had been made refractory to TPA by prolonged exposureto high concentrations remained sensitive to inhibition by phospholipaseC and OAG. These results suggest either that diacylglycerolcan produce other effects independent of protein kinase C activation,or that refractoriness to phorbol esters is not simply due toa decrease in the amount of protein kinase C. 相似文献
43.
44.
The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer’s disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood–brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer’s risk reduction. 相似文献
45.
46.
Klaus Pnicke Ingrid Heinroth-Hoffmann Karin Becker Otto-Erich Brodde 《British journal of pharmacology》1997,121(1):118-124
- Angiotensin II (AII) and the endothelins (ET) are known to be potent trophic stimuli in various cells including cardiomyocytes. In order to characterize further these effects we studied, in neonatal rat ventricular cardiomyocytes, the effects of several endothelin-receptor antagonists and the AT1-receptor antagonist losartan on AII- and endothelin-induced inositol phosphate (IP)-formation (assessed as accumulation of total [3H]-IPs in myo-[3H]-inositol prelabelled cells) and increase in rate of protein synthesis (assessed as [3H]-phenylalanine incorporation).
- Endothelin (10 pM–1 μM) concentration-dependently increased IP-formation (max. increase at 100 nM ET-1: 130±14% above basal, n=25) and [3H]-phenylalanine incorporation (max. increase at 1 μM: 52±4% above basal, n=16) with an order of potency: ET-1>>ET-3. Both effects were antagonized by the ETA/ETB-receptor antagonist bosentan and the ETA-receptor antagonist BQ-123, but not affected by the ETB-receptor antagonist IRL 1038 and the AT1-receptor antagonist losartan.
- Pretreatment of the cells with 500 ng ml−1 pertussis toxin (PTX) overnight that completely inactivated PTX-sensitive G-proteins did not attenuate but rather enhance ET-1-induced IP-formation. On the other hand, in PTX-pretreated cardiomyocytes ET-1-induced [3H]-phenylalanine incorporation was decreased by 39±5% (n=5).
- AII (1 nM–1 μM) concentration-dependently increased IP-formation (max. increase at 1 μM: 42±7% above basal, n=16) and [3H]-phenylalanine incorporation (max. increase at 1 μM: 29±2%, n=9). These effects were antagonized by losartan, but they were also antagonized by bosentan and BQ-123.
- In well-defined cultures of cardiomyocytes (not contaminated with non-myocyte cells) AII failed to increase [3H]-phenylalanine incorporation; addition of non-myocyte cells to the cardiomyocytes restored AII-induced increase in [3H]-phenylalanine incorporation.
- We conclude that, in rat neonatal ventricular cardiomyocytes, (a) the ET-1-induced increase in rate of protein synthesis (through ETA-receptor stimulation) involves at least two signalling pathways: one via a PTX-insensitive G-protein coupled to IP-formation, and the other one via a PTX-sensitive G-protein, and (b) the trophic effects of AII are brought about via local ET-1 secretion upon AT1-receptor stimulation in neonatal rat ventricular non-myocyte cells.
47.
Swedish guidelines for early childhood education emphasize the importance of children's existential questions. The program encourages preschool to offer children different opportunities to work on questions like what it is to be, to live and die, grow old, about religion, beliefs, traditions, etc. at their level of maturity (Social-styrelsen, 1987). Our experience in teacher education and early childhood programs is, however, that this is an area in which many teachers have difficulties. In the present empirical study 13 teachers were interviewed to find outwhat they consider existential questions for their children to be, and whatstrategies or methods they have for dealing with these questions. Teachers' conceptions about the what and how aspects of existential questions are described in terms of their qualitative differences. Each teacher was then asked to keep a diary of the existential questions children raised during the following month. Differences between the teachers' conceptions, which showed hesitation, and the spontaneous approaches and active involvement that emerged in reality, as recorded in their own diaries, are discussed. 相似文献
48.
Øystein Bruserud Ingrid Nesthus Graham Pawelec 《Cancer chemotherapy and pharmacology》1995,37(1-2):70-78
The in vitro effect of the dextroisomer r-verapamil on blast cells derived from patients with acute myelogenous leukemia (AML) was studied. R-verapamil caused a dose-dependent inhibition of AML blast proliferation in the presence of stem-cell factor, leukemia inhibitory factor, interleukin 4, interleukin 6, and interleukin 10 when these cytokines were tested both alone and in different combinations. R-verapamil also inhibited the growth of clonogenic AML blast cells. The antiproliferative effect was not specific for AML blast cells, because r-verapamil also inhibited cytokine-dependent proliferation of blast cells derived from patients with acute lymphoblastic leukemia. The inhibitory effects of r-verapamil and anti-IL1 serum were additive, suggesting that the antiproliferative effect of r-verapamil does not depend solely on inhibition of IL1-mediated effects. Although r-verapamil inhibited spontaneous AML blast proliferation, for a majority of patients it caused only minimal, if any, inhibition of spontaneous cytokine secretion (IL1, IL1, TNF, IL6) by AML blast cells. Thus, although inhibition of IL1 effects may contribute in certain patients to the antiproliferative effect of r-verapamil, mechanisms other than IL1 inhibition seem to be more important in mediating the effects of r-verapamil.Abbreviations
ALL
Acute lymphocytic leukemia
-
AML
acute myelogenous leukemia
-
cpm
counts per minute
-
ELISA
enzyme-linked immunosorbent assay
-
G-CSF
granulocyte colony-stimulating factor
-
GM-CSF
granulocyte-macrophage colony-stimulating factor
-
IL
interleukin
-
IF
leukemia inhibitory factor
-
PBMC
peripheral blood mononuclear cells
-
RR
relative response
-
SCF
stem cell factor
-
TNF
tumor necrosis factor 相似文献
49.
Cyclosporine is a powerful immunosuppressant with a narrow therapeutic window and considerable inter- and intrapatient variability.
The pre-dose trough concentration (Cmin) is commonly used for therapeutic drug monitoring. With the new microemulsion (Neoral), intrapatient variability was reduced.
However, the usefulness of Neoral Cmin was questioned. Firstly, because of the improved and more-rapid absorption, accidental intake before blood sampling has a
greater impact on Cmin than with classic cyclosporine. Secondly, Cmin may be low despite high drug exposure, due to rapid clearance in children. A full pharmacokinetic (PK) profile with determination
of the area under the curve (AUC) is expensive and cumbersome, and therefore a search for an abbreviated AUC began. Here,
we present a retrospective analysis of 84 PK profiles from 78 pediatric renal transplant recipients. By analysis of rejection
episodes and toxicity, we estimated a target AUC above 5,000 ng×h/ml in the early post-transplant period and 3,900 ng×h/ml
beyond 100 days. The abbreviated AUC using the 2- and 6-h concentrations (C2 and C6) and a simple estimate derived from the
3-h concentration (C3) were equally well correlated with the AUC. From our data, we recommend a target C3 at approximately
800 ng/ml early after transplantation and 450–550 ng/ml beyond 100 days.
Received: 28 January 1998 / Revised: 10 June 1998 / Accepted: 15 June 1998 相似文献
50.
Nonoperative Management of Primary Colorectal Cancer in Patients With Stage IV Disease 总被引:12,自引:0,他引:12
Scoggins CR Meszoely IM Blanke CD Beauchamp RD Leach SD 《Annals of surgical oncology》1999,6(7):651-657
Background: Traditional teaching maintains that patients with primary colorectal adenocarcinoma require timely resection to prevent bleeding, perforation, or obstruction. The true benefits of primary tumor resection remain undocumented for patients presenting with metastatic disease, however. We postulated that resection of primary colorectal tumors could be avoided safely in a select population of asymptomatic colorectal cancer patients presenting with incurable stage IV disease.Methods: A retrospective review of the Vanderbilt University Hospital tumor registry was performed for the years 1985 to 1997. During this period, 955 patients presented for management of primary colorectal cancer. From this group, all patients with stage IV disease at the time of diagnosis were identified. Patients who initially underwent resection of their primary lesion were included in the resection group; those who underwent initial nonoperative primary tumor management were included in the nonresection group. Data were obtained regarding age, extent of disease, nonsurgical therapy, tumor-specific complications, and palliative surgical procedures. Surgery-free survival and overall survival were analyzed using the Kaplan-Meier method. For patients with liver metastases, hepatic tumor burden was defined as either H1 (<25% parenchymal replacement), H2 (25% to 50%), or H3 (>50%) disease.Results: Sixty-six patients were included in the resection group, and 23 patients with intact asymptomatic primary colorectal lesions were included in the nonresection group. Among patients with hepatic metastases, most of the patients in both groups had H1 disease. Ten patients in the resection group and 3 patients in the nonresection group presented with exclusively extrahepatic metastases. In the nonresection group, primary therapy included chemotherapy in 13 patients, external beam radiation therapy in 1 patient, and combination chemoradiation in 9 patients. The median survival in the nonresection group was 16.6 months. The 2-year actuarial survival was 18%, and the surgery-free survival was 91.3%. Only 2 of 23 patients (8.7%) managed without resection eventually developed obstruction at the primary tumor site requiring emergent diversion. There were no episodes of tumor-related hemorrhage or perforation. For the resection group, the operative morbidity was 30.3%, and the perioperative mortality rate was 4.6%. The median survival in the resection group was 14.5 months (P = 0.59, log-rank test vs. nonresection group).Conclusions: Selected patients with asymptomatic primary colorectal tumors who present with incurable metastatic disease may safely avoid resection of their primary lesions, with an anticipated low rate of hemorrhage, perforation, or obstruction before death from systemic disease. No survival advantage is gained by resection of an asymptomatic primary lesion in the setting of incurable stage IV colorectal cancer. 相似文献