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991.
Aitor Uribarri Sebastian V. Rojas Jasmin S. Hanke Günes Dogan Thierry Siemeni Tim Kaufeld Fabio Ius Tobias Goecke Sara Rojas-Hernandez Gregor Warnecke Christoph Bara Murat Avsar Axel Haverich 《Revista espa?ola de cardiología》2019,72(8):608-615
Introduction and objectivesMalnutrition has been shown to affect clinical outcomes in patients with heart failure. The aim of this study was to analyze the impact of preoperative nutritional status assessed by the nutritional risk index (NRI) on the prognosis of patients with a continuous-flow left ventricular assist device (cf-LVAD).MethodsWe performed a retrospective study of 279 patients who underwent cf-LVAD implantation between 2009 and 2015 in our center. Preoperative NRI was calculated and the patients were followed-up for 1 year. The association between preoperative NRI and postoperative clinical events was analyzed using multivariable logistic regression.ResultsThe prevalence of severe (NRI < 83.5), moderate (83.5 ≤ NRI < 97.5) and mild (97.5 ≤ NRI < 100) nutritional risk was 5.4%, 21.5%, and 9.3%. Mortality rates 1 year after cf-LVAD implantation in these 3 categories were 53.3%, 31.7%, 23.1% vs 18.0% (P < .001) in patients with a normal IRN. A normal preoperative NRI value was an independent predictor of lower risk of death from any cause during follow-up (aHR per 1 unit, 0.961; 95%CI, 0.941-0.981; P < .001) was and a predictor for a lower risk of postoperative infections (aOR, 0.968; 95%CI, 0.946-0.991; P = .007), respiratory failure (aOR, 0,961; 95%CI, 0.936-0.987; P = .004), and right heart failure (aOR, 0.963; 95%CI, 0.934-0.992; P = .014).ConclusionsMalnourished patients are at increased risk for postoperative complications and death after cf-LVAD implantation. Assessment of nutritional risk could improve patient selection and the early initiation of nutritional support.Full English text available from: www.revespcardiol.org/en 相似文献
992.
The case report describes the occlusal rehabilitation of a male patient with Angle Class III malocclusion and its effect on maximum bite force. The main complaints of patient were masticatory difficulty and poor esthetic. The patient''s expectations from the treatment were a good esthetic and function with a less invasive and relatively promptly way. Therefore, increasing of the occlusal vertical dimension (OVD) and then restoring the maxillary and mandibular teeth was chosen by the patient among the treatment options. At the beginning of treatment maximum bite force of patient was measured. Then an occlusal splint was provided to evaluate the adaptation of the patient to the altered OVD. Full mouth rehabilitation with metal ceramic restorations was made. After the completion of full mouth restoration, bite force measurement was repeated and patient exhibited increased maximum bite force. Full mouth restorative treatment in a patient with Class III malocclusion could be an effective treatment approach to resolve esthetic concern and to improve masticatory function related to maximum bite force. 相似文献
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Attenuated coronary flow reserve (CFR) has been reported in patients with idiopathic dilated cardiomyopathy (IDC). On the other hand increased platelet activity has been demonstrated in patients with congestive heart failure and left ventricular dysfunction. Accordingly, we aimed to investigate whether mean platelet volume (MPV) is increased in patients with IDC and increased MPV correlates with the degree of coronary microvascular dysfunction. MPV was measured in 37 patients with IDC. Each patient with IDC also underwent echocardiographic examination including CFR measurement. Patients with IDC were divided into two groups based on median CFR value (lower CFR group and normal CFR group). MPV was significantly higher in the lower CFR group than in the normal CFR group (9.00?±?0.56 vs. 8.25?±?0.76 ?; respectively, p?=?0.001). CFR correlated significantly and inversely to MPV (r?=?-0.475, p?=?0.003). Logistic regression analysis revealed that MPV level was the independent predictor of lower CFR (β?=?-0.750, p?=?0.002). Furthermore, MPV was an accurate predictor of low CFR (p?=?0.001); Area under the curve was 82% (95% CI 0.67-0.96). The best cut-off value of MPV to predict low CFR was 8.3 fl with 95% sensitivity and 69% specificity. In conclusion, the present study showed a negative correlation between MPV and CFR in patients with IDC. 相似文献
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An ultrafast and convenient method for PEGylation of chitosan nanoparticles has been established through a photopolymerization reaction between the acrylate groups of PEG and methacrylated-chitosan nanoparticles. The nanoparticle characteristics under physiological pH conditions were optimized through altered PEG chain length, concentration and duration of UV exposure. The method developed here has potential for clinical translation of chitosan nanoparticles. It also allows for the scalable and fast synthesis of nanoparticles with colloidal stability.An ultrafast and convenient method for PEGylation of chitosan nanoparticles has been established through a photopolymerization reaction between the acrylate groups of PEG and methacrylated-chitosan nanoparticles.The latest progress regarding the framework of bioengineered nanoparticles has led to the development of new biodegradable nanoparticles for potential treatment purposes.1–6 Recent methods in nanomedicine have leaned towards developing colloidally stable, biocompatible nanoparticles which can overcome biological barriers without causing any harm to living tissues. Accordingly, the surface charge and size optimization of such particles has gained great importance as they are major factors for the stability of the system.7The search for bioadhesive nanoparticles that have potential as clinically viable materials extends to a wide scope in the field. One such material is chitosan, which has an application range including food, cosmetics and biomedicine.8–11 As this material is known for its biocompatible,12 biodegradable13 and nontoxic nature, it becomes an expedient choice to be used for therapeutic purposes such as drug or gene delivery.14–16 Moreover, the reaction of primary amines attached to chitosan backbone permit functionalization of this material with photosensitive groups. One of those functionalization is the addition reaction of the amino groups with methacrylic anhydride which produces photosensitive methacrylamide groups.17,18 This modification of chitosan chains allows for photocrosslinking of this adhesive monomer in the presence of a photo initiator under UV light to form a gel.19Multiple methods are present to synthesize chitosan nanoparticles such as reverse micellar,20 emulsification solvent diffusion,21 and ionotropic gelation method.22,23 Chitosan nanoparticles have been synthesized at acidic pH due to the presence of negatively charged sodium tripolyphosphate (TPP) and cationic chitosan chains, within a short time at room temperature through ionic gelation.14 Majority of research that involves the synthesis of these nanoparticles consider the size and zeta potential of chitosan nanoparticles between pH 4.0 and 5.5, where these methods do not characterize the properties at physiological conditions regardless of this major applicability constraint.24,25 To overcome this obstacle, we have developed a unique PEGylation approach which can be utilized for wide ranges of pH without compromising the solution stability of chitosan. For this reason, PEGylation may be considered as a critical route for advancing chitosan nanoparticles as biomedical tools and making the particle system colloidally stable.26 There are various approaches used for the PEGylation of chitosan nanoparticles such as the PEGylation of chitosan chains prior to nanoparticle synthesis.27,28 However, these existing methods used for direct chemical conjugation of PEG to chitosan are time consuming, require complex reactions and equipment. In our work, we address two fundamental issues for the utilization of chitosan nanoparticles in biomedicine: (i) optimization of chitosan nanoparticle properties at physiological pH, and (ii) development of a novel PEGylation method for chitosan nanoparticles for long term feasibility and large-scale synthesis.The novel method we introduce here for the PEGylation of chitosan overcomes the limitations associated with the use of chitosan nanoparticles in biomedicine. We prepare ionically crosslinked and PEGylated chitosan nanoparticles through simultaneous addition of photoinitiator with TPP and acrylate-PEG prior to UV light exposure at 365 nm, which promotes covalent bond formation between the acrylate groups of PEG and methacrylamide chitosan nanoparticles (CSMA) (Fig. 1). Methacrylamide chitosan was synthesized according to previously described protocol.17–19 (ESI Experimental section 2†). Synthesis of methacrylamide chitosan is a scalable one-step process and allows for the large amounts of product formation. Two groups of methacrylamide chitosan chains were prepared for the optimization of degree of methacrylation during nanoparticle formation: chitosan functionalized with (1) 50 μL and (2) 100 μL methacrylic anhydride (MA) per 30 mg of chitosan. Aggregation was observed inside the CSMA solution with the higher methacrylation degree (100 μL MA to 30 mg chitosan) for different groups at pH 4.7 (Table S1†). Hence, we continued our experiments with the methacrylamide chitosan polymer that has lower degree of methacrylation. It was possible to obtain nanoparticles with high colloidal stability using the less methacrylated-chitosan polymer with sub 100 nm size and positive charge at pH 4.7 (Open in a separate windowFig. 1Overall strategy for the new method. (A) Synthesis of methacrylamide chitosan from chitosan. (B) Nanoparticle synthesis via ionic gelation method. Interaction between positively charged methacrylamide chitosan and negatively charged TPP crosslinker form nanoparticles. (C) PEGylation of methacrylamide chitosan nanoparticles. UV light triggers the reaction between methacrylic groups on nanoparticles and acrylate-PEG derivative in the presence of photoinitiator. PEGylated nanoparticles are obtained under optimized conditions.Size, PDI and zeta potential of different group of nanoparticles
Open in a separate windowaNumber of PEG mole per 25 mg of chitosan nanoparticle solution.bAggregated.Degree of methacrylation for the less methacrylated polymer (50 μL MA to 300 mg chitosan) was calculated with 2,4,6-trinitrobenzenesulfonic acid (TNBS) assay, where 20% of amino groups were converted into photosensitive methacrylamide groups. However, this group of methacrylamide chitosan nanoparticles had no colloidal stability and aggregated irreversibly at pH 7.4 (†). Then, we decreased LAP amount by tenfold, from 69 μL to 6.9 and 1 μL, and observed no aggregation at pH 4.7 with 1 and 10 min of UV light exposure for both groups (Table S1, Samples 4 and 10†). Accordingly, we prepared five different nanoparticle solutions of 12.5 mL which contained 6.9 μL of LAP and 7 μmoles of 5 kDa acrylate-PEG. Next, we exposed these solutions to UV light for altered durations of 0, 1, 5, 10 and 20 minutes. For these groups, no aggregation was observed at pH 4.7. However, for the groups that were exposed to 0, 1, and 5 minutes of UV, aggregations were visible at pH 7.4, probably due to no or insufficient PEGylation reaction. On the other hand, the groups that were exposed to 10 and 20 minutes of UV light did not aggregate at pH 7.4 (ESI, Table S1†). The solutions of these groups of 10 and 20 minutes of UV exposure were observed as clear at pH 7.4, which was a direct indication for successful PEGylation. The group that had 1 μL LAP solution aggregated at pH 7.4 probably due to insufficient PEGylation (ESI, Table S1, Sample 11†). We also investigated the direct effect of LAP initiator to the PEGylation, and the group without initiator aggregated at pH 7.4 (ESI, Table S1, Sample 12†). We measured larger particle sizes for the group that was exposed to UV for 20 minutes, probably due to crosslinking of nanoparticles (Fig. S1 and S2†). From these results, we concluded that 6.9 μL LAP and 10 min UV exposure conditions are optimal for fast and simple PEGylation of nanoparticles.Thus, this condition was utilized for the following experimental trials. We used 5 kDa and 10 kDa chain lengths of PEG for the PEGylation of chitosan nanoparticles. Six different conditions of 4, 7 and 10 μmoles of 5 kDa and 10 kDa PEG were used per 5 mg of chitosan nanoparticle solution in different trials as was presented in 27 We were able to obtain nanoparticles with decreasing surface charge at pH 7.4 for 5 kDa groups. This also means that, it is possible to tune the surface charge of nanoparticles to some extent. However, increasing the amount of PEG to decrease surface charge of nanoparticles resulted in aggregation.These aggregations can be due to the tangling of free and conjugated PEG on the surface of the nanoparticles which stay closer to each other at increased pH levels due to ionic attraction forces as is shown schematically in Fig. 2. This effect was more obvious in 10 kDa groups since longer chains induces more entanglement in the solution (†). These results suggest that PEGylated chitosan nanoparticles are non-toxic to HEK293-T cells at high doses.Open in a separate windowFig. 2Illustration for the aggregation behaviour observed in high PEG mole or PEG chain length groups. At low pH, particles are stable due to strong repulsion force. At higher pH values, nanoparticles tend to be close to each other due to lower repulsion effects. This tendency results in the aggregation of nanoparticles induced by entanglement of conjugated and free PEG macromolecules.Presence of PEG in the PEGylated chitosan nanoparticles was confirmed via FTIR analysis and results are shown in Fig. S4.† PEGylated chitosan nanoparticles were dialyzed to eliminate the unreacted PEG macromolecules. FT-IR spectrum of PEGylated chitosan nanoparticles retained C–H stretches around 2800 cm−1 and amine stretches around 1639 cm−1, which further confirmed PEGylation of nanoparticles. Moreover, scanning electron microscopy (SEM) image was examined to visualize these nanoparticles as presented in Fig. S5–S7.† The particle characterization results indicated an increasing trend in particle sizes and a decreasing trend in observed zeta potentials with increasing molecular weight of PEG due to the increased number of conjugated PEG chains on the surface of the nanoparticles.In summary, a new and simple PEGylation method has been introduced in this study, through photopolymerization of functional photosensitive groups of chitosan. This method has shown to be significant as it is achieved within minutes and does not involve complex equipment compared to the existing PEGylation of chitosan methods. The results suggest that particles synthesized using this approach are non-toxic and colloidally stable under physiological pH condition. The optimization of nanoparticle characteristics for different UV exposure durations, PEG chain lengths and concentrations has proven that the desired characteristics for PEGylated chitosan nanoparticles can be achieved under different conditions combinations. It has been concluded that the simultaneous increase in PEG chain length and concentration in nanoparticle solution should be avoided as free and conjugated PEG chains might promote chain entanglements with shorter intermolecular distances at physiological pH. This new method can be used for the realistic biomedical applications of chitosan nanoparticles and offers scalable and fast fabrication of colloidally stable nanoparticles. 相似文献
Sample name | PEG MW (kDa) | PEG molea (μmole) | pH | UV | Observed size (nm) | Polydispersity index | Observed zeta potential (mV) |
---|---|---|---|---|---|---|---|
Negative control 1 | — | — | 4.7 | No | 90.75 ± 0.56 | 0.383 ± 0.05 | 32.3 ± 4.34 |
Negative control 2 | — | — | 7.4 | No | Agg.b | Agg.b | Agg.b |
1 | 5 | 4 | 4.7 | Yes | 83.97 ± 1.00 | 0.297 ± 0.08 | 32.2 ± 3.80 |
2 | 5 | 4 | 7.4 | Yes | 136.30 ± 6.85 | 0.118 ± 0.01 | 6.01 ± 3.14 |
3 | 5 | 7 | 4.7 | Yes | 88.38 ± 0.56 | 0.390 ± 0.28 | 31.8 ± 6.94 |
4 | 5 | 7 | 7.4 | Yes | 120.06 ± 6.91 | 0.230 ± 0.02 | 4.23 ± 3.36 |
5 | 5 | 10 | 4.7 | Yes | 89.31 ± 0.80 | 0.411 ± 0.01 | 31.9 ± 4.41 |
6 | 5 | 10 | 7.4 | Yes | Agg.b | Agg.b | Agg.b |
7 | 10 | 4 | 4.7 | Yes | 91.93 ± 1.33 | 0.424 ± 0.01 | 30.7 ± 3.82 |
8 | 10 | 4 | 7.4 | Yes | 189.56 ± 11.87 | 0.145 ± 0.01 | 5.64 ± 3.20 |
9 | 10 | 7 | 4.7 | Yes | 83.55 ± 4.03 | 0.466 ± 0.01 | 30.2 ± 4.05 |
10 | 10 | 7 | 7.4 | Yes | Agg.b | Agg.b | Agg.b |
11 | 10 | 10 | 4.7 | Yes | 60.82 ± 0.10 | 0.496 ± 0.01 | 28.6 ± 3.76 |
12 | 10 | 10 | 7.4 | Yes | Agg.b | Agg.b | Agg.b |
999.
Bulent Oguz Genc Ebru Apaydın Dogan Umuttan Dogan Emine Genc 《Journal of clinical neuroscience》2010,17(10):1256-1259
We aimed to investigate the effects of topiramate monotherapy on anthropometric indexes, insulin resistance, and serum leptin and lipid levels in 33 premenopausal women (mean age ± standard deviation: 26.7 ± 7.1 years) with cryptogenic epilepsy. Body mass index (BMI), waist circumference and serum leptin, insulin and lipid levels were measured at baseline and at 6 months after initiation of topiramate. We found reductions in BMI (p < 0.001), waist circumference (p < 0.001) and serum high-density lipoprotein (HDL) cholesterol levels (p = 0.011). We also found significant improvements in insulin resistance (p = 0.023), but not in serum leptin levels (p = 0.45). Our results suggest that topiramate treatment in women with epilepsy is associated with reduced BMI and waist circumference and improvement in insulin resistance; however, according to our data, topiramate treatment is also associated with lower HDL cholesterol levels, which may substantially increase vascular disease. 相似文献
1000.