全文获取类型
收费全文 | 1670篇 |
免费 | 76篇 |
国内免费 | 41篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 45篇 |
妇产科学 | 13篇 |
基础医学 | 193篇 |
口腔科学 | 26篇 |
临床医学 | 267篇 |
内科学 | 558篇 |
皮肤病学 | 10篇 |
神经病学 | 42篇 |
特种医学 | 224篇 |
外科学 | 94篇 |
综合类 | 25篇 |
预防医学 | 120篇 |
眼科学 | 9篇 |
药学 | 96篇 |
肿瘤学 | 61篇 |
出版年
2023年 | 5篇 |
2022年 | 5篇 |
2021年 | 17篇 |
2020年 | 16篇 |
2019年 | 16篇 |
2018年 | 27篇 |
2017年 | 20篇 |
2016年 | 14篇 |
2015年 | 17篇 |
2014年 | 37篇 |
2013年 | 36篇 |
2012年 | 51篇 |
2011年 | 57篇 |
2010年 | 49篇 |
2009年 | 69篇 |
2008年 | 87篇 |
2007年 | 103篇 |
2006年 | 78篇 |
2005年 | 83篇 |
2004年 | 55篇 |
2003年 | 51篇 |
2002年 | 36篇 |
2001年 | 38篇 |
2000年 | 44篇 |
1999年 | 41篇 |
1998年 | 61篇 |
1997年 | 54篇 |
1996年 | 46篇 |
1995年 | 38篇 |
1994年 | 27篇 |
1993年 | 40篇 |
1992年 | 35篇 |
1991年 | 29篇 |
1990年 | 24篇 |
1989年 | 46篇 |
1988年 | 37篇 |
1987年 | 43篇 |
1986年 | 33篇 |
1985年 | 28篇 |
1984年 | 23篇 |
1983年 | 24篇 |
1982年 | 18篇 |
1981年 | 22篇 |
1980年 | 24篇 |
1979年 | 8篇 |
1978年 | 16篇 |
1977年 | 17篇 |
1976年 | 12篇 |
1975年 | 9篇 |
1968年 | 4篇 |
排序方式: 共有1787条查询结果,搜索用时 15 毫秒
31.
Romieu R; Lacabanne V; Kayibanda M; Antoine B; Bennoun M; Chouaib S; Guillet JG; Viguier M 《International immunology》1997,9(10):1405-1413
There is now good evidence that cytokines contribute to the regulation of
tumor growth. The cytokine-driven modulation of tumor growth was
investigated during the progression of a hepatocellular carcinoma (HCC) in
SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of
liver growth correlated with increased transforming growth factor
(TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis
factor (TNF)-alpha mRNA were detected earlier during tumor development.
Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2,
IL-4 and IFN-gamma mRNA production could be reported. In vitro,
hepatocyte-like tumor cell lines established at two stages, either before
or after HCC differentiation, were characterized. The early-stage-derived
cell line produced TNF-alpha mRNA, but had barely detectable expression of
TGF-beta 1 mRNA, while later-stage- derived cell lines showed the
reciprocal pattern. All cell lines displayed a lack of sensitivity to
TNF-alpha, although some degree of sensitivity to TNF-alpha could be
observed in the presence of actinomycin-D or after treatment with
IFN-gamma. The early-stage- derived cell line was sensitive to the growth
inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines
displayed a loss of sensitivity to TGF-beta 1 which correlated with the
increased expression of TGF-beta 1 mRNA. Altogether, this suggests that
tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression
patterns during HCC progression. This model of HCC could be of valuable
interest to assess the impact of various immunotherapeutic strategies on
modulation of tumor growth.
相似文献
32.
J. Zweens Henny Frankena A. Reicher W. G. Zijlstra 《Pflügers Archiv : European journal of physiology》1980,385(1):71-77
The determination of D2O in biological fluids by means of infrared spectrometry was reinvestigated. When the temperature of a solution, containing D2O in the range from natural abundance to 5 ml·1–1 increases, its absorbance decreases and the wavenumber of maximum absorption shifts to a higher value. Both changes are linearly related to the change in temperature. Storage for 17 d in either glass or polyethylene tubes does not affect the D2O concentration. Purification of biological fluids by vacuum-sublimation removes all substances which also absorb at the O-D vibration band and the recovery of D2O from plasma and urine is complete. The partition ratio of D2O between plasma water and red cell water equals unity, and the same holds for plasma water and urine water over a wide range of urine flows and osmolalities. The arterial and urinary disappearance curves of D2O, measured over several days, both permit the calculation of the total amount of body water (V
bw), the daily water turn-over (F) and the half-time of water in the body (t
1/2), but the data derived from arterial disappearance curves are more precise. In 16 male mongrel dogs (25–32 kg body mass) the following results were obtained:V
bw=626±28 ml·kg–1,F=12.0±3.2% andt
1/2=6.21±1.78 d. 相似文献
33.
Ren A Tio Jasper S Wijpkema Eng S Tan Folkert W Asselbergs Geke A P Hospers Gillian A J Jessurun Felix Zijlstra 《Endothelium》2005,12(3):103-106
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF gene therapy improves perfusion of ischemic myocardium in experimental models and possibly in patients with end-stage coronary artery disease. In addition to its proliferative and migratory effect on endothelial cells, it also activates and up-regulates endothelial nitric oxide synthase (eNOS). Therefore, the authors investigated coronary endothelium-dependent vasodilatation in patients before and after VEGF gene therapy. The effect of intracoronary acetylcholine infusion on coronary diameter was assessed at baseline and after 3 months follow-up in patients with end-stage coronary artery disease treated with VEGF gene and in controls scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) (acetylcholine test at diagnostic angiography and before a subsequently scheduled PTCA). Five out of six VEGF patients experienced a reduction in anginal complaints. Angiographic evidence for improved collateral filling was evident in two out of six patients. The vasoconstrictive response to acetylcholine was partly converted into dilatation. In contrast, the acetylcholine response in control patients remained vasoconstrictive. In conclusion, VEGF gene therapy has an important beneficial effect on the functional characteristics of the myocardial vascular network. Therefore, this therapy can potentially play an important role in all stages of the atherosclerotic process. 相似文献
34.
Y. L. Hoogeveen J. P. Zock P. Rispens W. G. Zijlstra 《Pflügers Archiv : European journal of physiology》1987,410(3):257-262
While maintaining the arterial CO2 tension constant near the normal level of the dog (4.3 kPa), we studied the influence of decreasing cardiac output on both the arterial and mixed-venous blood acid-base status in anaesthetized, artificially ventilated dogs. Cardiac output was manipulated by applying positive end-expiratory pressure (PEEP), and by -adrenergic blockade to suppress a compensatory heart rate response. The systemic vascular response was attenuated by -adrenergic blockade. Metabolic rate remained virtually unchanged when cardiac output decreased. Under these conditions a fall in cardiac output led to a shift of the arterial acid-base status in the direction of a metabolic acidosis. The changes occurring in the mixed-venous blood resembled those of an in-vivo CO2 bufferline, with the shift being such as if a respiratory acidosis was developing. 相似文献
35.
Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule
下载免费PDF全文
![点击此处可从《The British journal of general practice》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Bianca LW Bendermacher Joep AW Teijink Edith M Willigendael Marie-Louise Bartelink Harry R Büller Ron JG Peters Jelis Boiten Machteld Langenberg Martin H Prins 《The British journal of general practice》2006,56(533):932-937
BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease. 相似文献
36.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
37.
J. Zweens Henny Frankena W. G. Zijlstra 《Pflügers Archiv : European journal of physiology》1978,376(2):131-138
The effect of pentobarbital anaesthesia on the volume and ionic composition of the extracellular space was studied in adult male mongrel dogs with permanent catheters in aorta and pulmonary artery. The extracellular fluid volume (Q
ec
) was determined with: a) methods based on equilibration of the indicator throughoutQ
ec
by continuous infusion; b) methods based on the assumption that after a single injection of indicator the plasma indicator concentration equals extracellular indicator concentration as long as the log plasma indicator concentration-time curve is linear; c) a single injection method based on a closed flow system model with a single inflow and a single outflow orifice. The measurements were made before and 30 and 90 min after induction of anaesthesia. Thirty minutes after induction of anaesthesiaQ
ec
as determined with the method sub a, had decreased by about 10% and remained so during the following 60 min. The values ofQ
ec
as calculated by the method sub c fairly agreed withQ
ec
as determined with the method sub a and also showed a decrease ofQ
ec
during pentobarbital anaesthesia. The procedures sub b overestimatedQ
ec
and yielded a seemingly higherQ
ec
during anaesthesia, because the boundary conditions for these procedures do not apply. The haemoglobin concentration decreased by about 10% and the lactate concentration by about 50%. The phosphate concentration increased by about 25% while the other electrolyte concentrations (Na+, K+, Mg2+, Ca2+, Cl–, HCO
3
–
) did not change. A respiratory acidosis developed during the first 30 min and almost disappeared in the following 60 min. Possible explanations for the pentobarbital-induced concentration ofQ
ec
are discussed. 相似文献
38.
A. J. M. Langbroek A. Nijmeijer P. Rispens W. G. Zijlstra 《Pflügers Archiv : European journal of physiology》1990,417(2):157-160
Arterial pH and blood gases were measured at intervals in conscious dogs after their first human contact of the day. Blood was sampled through an indwelling catheter in the aorta without disturbing the animals. It appeared that in the first 90 min arterial PO2, oxygen saturation and haemoglobin concentration significantly declined. PCO2 and pH changed less consistently when the acid/base status of the dogs was normal, but when a non-respiratory acidosis was present there was a significant decrease in pH and a significant increase in PCO2. Arterial pH and blood gases were also measured before and after feeding the animals. It appeared that an appreciable metabolic alkalosis developed within 2 h after a meal. The alkaline tide was accompanied by a trend to higher values for PCO2. It is concluded that, after a period of seclusion, renewed human contact causes behavioural changes in a dog, which may result in appreciable transitory changes in arterial pH and blood gas values. Blood sampling from conscious dogs should therefore take place after a proper period of habituation; preferably, a few samples should be taken at intervals to check that a steady state has been reached. If possible, blood should be collected before feeding; in any case the relationship in time of blood sampling to feeding should be constant throughout. 相似文献
39.
Ecotropic and dualtropic mink cell focus-inducing murine leukemia viruses can induce a wide spectrum of H-2 controlled lymphoma types 总被引:5,自引:0,他引:5
Neonatal infection of C57BL and BALB/c mice by cloned ecotropic and dualtropic mink cell focus-inducing (MCF) murine leukemia viruses (MuLV) induces a wide spectrum of different lymphomas of T, B, and non-T/non-B cell types. Oncogenic dualtropic MCF viruses and poorly oncogenic ecotropic MuLV act synergistically in lymphomagenesis. Within one mouse strain virus-induced T-cell lymphomas arise earlier than B-cell lymphomas after neonatal inoculation of a single-cloned MuLV. The host genetic constitution, notably the H-2 complex has a marked influence on lymphoma type. This H-2 influence can be explained by an H-2-linked difference in penetration of the thymus early in life by oncogenic thymotropic MuLV, which in turn is correlated with, but not necessarily due to the magnitude of the anti-MuLV antibody response. 相似文献
40.
Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET) 总被引:2,自引:2,他引:0
John M. Bolster Willem Vaalburg Anne M. J. Paans Theo H. van Dijk Philip H. Elsinga Jan B. Zijlstra Do A. Piers Nanno H. Mulder Martien G. Woldring Hans Wynberg 《European journal of nuclear medicine and molecular imaging》1986,12(7):321-324
To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-11C)-tyrosine by 11C-carboxylation of the appropriate -lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-11C)-Tyrosine in 0.1 N NaH2PO4 buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-11C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-11C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma. 相似文献