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101.
Journal of Thrombosis and Thrombolysis - The purpose of the currents study was to enhance bioavailability of rivaroxaban (RXB) and reduce the food effect. RXB loaded PLGA nanoparticles...  相似文献   
102.
Globally, abortion has emerged as a critical determinant of maternal morbidity and mortality. The Ghana government amended the country's abortion law in 1985 to promote safe abortion. This article discusses the findings of a qualitative study that explored the decision-making experiences of 28 female abortion seekers aged between 15 and 30 years in Ghana. Key findings from the study are that individuals claimed autonomy in their abortion decisions; underlying the abortion decisions were pragmatic concerns such as economic difficulties, child spacing, and fear of parental reaction. In conclusion, we examine the health implications of Ghanaian women's abortion decisions.  相似文献   
103.
Innexins in invertebrates are considered to play roles similar to those of connexins and pannexins in vertebrates. However, it remains poorly understood how innexins function in biological phenomena including their function in the nervous systems. Here, we identified inx‐4, a member of the innexin family in C. elegans, by a forward screening of thermotaxis‐defective mutants. The inx‐4 mutants exhibited abnormal migration to a temperature slightly higher than the cultivation temperature, called mild thermophilic behavior. Rescue experiments revealed that INX‐4 acts in the major thermosensory neuron AFD to regulate thermotaxis behavior. INX‐4::GFP fusion protein localized exclusively along axons in AFD neurons. In addition, over‐expression of INX‐4 in AFD neurons induced a cryophilic behavior, which is opposite to inx-4 mutants. Our findings suggest that INX‐4/Innexin in AFD may fine‐tune the execution of thermotaxis behavior when moving to desired temperatures.  相似文献   
104.
The inflammatory response caused by scorpion venoms is a key event in the pathogenesis of scorpion envenomation. This response was assessed in the cardiac, pulmonary, and gastric tissues of envenomed mice. The results reveal an increase of permeability in cardiac, pulmonary, and gastric vessels accompanied by an edema-forming, inflammatory cell infiltration, and imbalanced redox status. These effects are correlated with severe tissue alterations and concomitant increase of metabolic enzymes in sera. Pretreatment of mice with antagonists of H1, H2, or H4 receptors markedly alleviated these alterations in the heart and lungs. Nevertheless, the blockade of the H3 receptor slightly reduced these disorders. Histamine H2 and H4 receptors were the most pharmacological targets involved in the gastric oxidative inflammation. These findings could help to better understand the role of histamine in scorpion venom-induced inflammatory response and propose new therapy using as targets the H4 receptor in addition to histamine H1 and H2 receptors to attenuate the induced inflammatory disorders encountered in scorpion envenoming.  相似文献   
105.
106.

Purpose

The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model.

Methods

Pregnant rats were exposed to nitrofen on embryonic day 9.5 (E9.5). MSCs were isolated from the enhanced green fluorescent protein (eGFP) transgenic rat lungs. The MSCs were transplanted into the nitrofen-induced E12.5 rats via the uterine vein, and the E21 lung explants were harvested. The study animals were divided into three: the control group, the nitrofen-induced left CDH (CDH group), and the MSC-treated nitrofen-induced left CDH (MSC-treated CDH group). The specimens were morphologically analyzed using HE and immunohistochemical staining with proliferating cell nuclear antigen (PCNA), surfactant protein-C (SP-C), and α-smooth muscle actin.

Results

The alveolar and medial walls of the pulmonary arteries were significantly thinner in the MSC-treated CDH group than in the CDH group. The alveolar air space areas were larger, while PCNA and the SP-C positive cells were significantly higher in the MSC-treated CDH group, than in the CDH group. MSC engraftment was identified on immunohistochemical staining of the GFP in the MSC-treated CDH group.

Conclusions

MSC transplantation potentially promotes alveolar and pulmonary artery development, thereby reducing the severity of pulmonary hypoplasia.  相似文献   
107.

Background/aim

Sodium is thought to be critical to growth. Infants who have an ileostomy may suffer from growth faltering, as sodium losses from stomas may be excessive. Urinary sodium measurements may indicate which patients could benefit from sodium supplementation; however, there is no consensus on what level of urinary sodium should be the cutoff for intervention. Our aim was to determine whether there is a relationship between urinary sodium and growth in infants undergoing ileostomy, colostomy and cystostomy.

Methods

Following audit approval, a retrospective observational study of patient notes and chemical pathology data was carried out. All infants <1 year of age that had an ileostomy, colostomy, or cystostomy procedure between February 1997 and January 2014 were included. Patients’ weights, urinary and serum sodium and potassium levels and clinical variables were recorded until discharge. Weights were converted to Z-scores for analysis.

Results

Forty patients were identified whose notes were available for review and who had at least three urinary sodium measurements. During their hospital stay, 11 (28 %) maintained weight within normal limits (Z-scores ?2 to +2, 15 (38 %) were moderately malnourished (?3 to ?2) and 14 (35 %) severely malnourished (30 mmol litre. Electrolyte data were not normally distributed so that correlations between electrolytes and growth were tested using the non-parametric Spearman rank correlation coefficient. Urinary sodium levels positively correlated with growth (r = 0.3071, p < 0.0001), as did serum sodium levels (r = 0.2620, p = 0.0059) whereas there was no relationship between urine or serum potassium and growth.

Conclusions

Poor growth is frequent in this group of patients and appears to be linked with sodium levels. Further work is necessary to draw up guidelines for appropriate sodium supplementation.  相似文献   
108.
Optimization of the ionomer materials in catalyst layers (CLs) which sometimes is overlooked has been equally crucial as selection of the membranes in membrane electrode assembly (MEA) for achieving a superior performance in proton exchange membrane fuel cells (PEMFCs). Four combinations of the MEAs composed of short-side-chain (SSC) and long-side-chain (LSC) perfluorosulfonic acid (PFSA) polymers as membrane and ionomer materials have been prepared and tested under various temperatures and humidity conditions, aiming to investigate the effects of different side chain polymer in membranes and CLs on fuel cell performance. It is discovered that SSC PFSA polymer used as membrane and ionomer in CL yields better fuel cell performance than LSC PFSA polymer, especially at high temperature and low RH conditions. The MEA with the SSC PFSA employed both as a membrane and as an ionomer in cathode CL demonstrates the best cell performance amongst the investigated MEAs. Furthermore, various electrochemical diagnoses have been applied to fundamentally understand the contributions of the different resistances to the overall cell performance. It is illustrated that the charge transfer resistance (Rct) made the greatest contribution to the overall cell resistance and then membrane resistance (Rm), implying that the use of the advanced ionomer in CL could lead to more noticeable improvement in cell performance than only the substitution as the membrane.  相似文献   
109.
110.
An addition of H-phosphonates to aryl alkynes was realized under solvent- and metal-free conditions, affording Markovnikov-selective α-vinylphosphonates in moderate to good yields. A wide range of aryl alkynes could be applied for the reaction. A tentative mechanism of addition–substitution was proposed based on in situ31P {1H} NMR studies.

Synthesis of α-vinylphosphonates from terminal alkynes and H-phosphonates as only the Markovnikov-regioisomer under metal- and solvent-free conditions.

Vinyl phosphorus compounds are of high importance because of their wide application in the fields of biological metabolism,1 functional materials,2 and as synthetic blocks of organophosphorus compounds.3 Some reviews have documented the preparations and applications of the vinyl phosphorus.4 Normally, the compounds can be acquired from alkynes, via the addition with H–P species. Aromatic ketones and aldehydes are also used as the sources of vinyl phosphorus, via multi-step conversions.1b,5 The recently developed methods to obtain vinyl phosphorus involving H–P species include decarboxylation of cinnamic acid,6 dehydrogenation of active alkene,7 and dehydration of alcohols.8The addition of H–P species to alkynes is undoubtedly the most effective and atom economical method. The addition was usually catalysed by metals.4e,9 One of the authors has reported palladium and rhodium catalysed additions of H–P species to alkynes.9ad Similar additions could be realized by catalysis with copper, nickel, molybdenum and ytterbium (Chart 1).10 The metal-catalysed procedures also include Suzuki reaction and others.11 Although much progress has been made in this area, problems associated with narrow substrate scope, the need to use expensive transition metals and a stoichiometric amount of additives, and poor regio- and stereo-control have encouraged researchers to search for new and more efficient methods.Open in a separate windowChart 1Comparison of the construction of C(sp2)–P bonds to our current work.Recently, triflic anhydride (Tf2O) has been applied for electrophilic activation of amides and P Created by potrace 1.16, written by Peter Selinger 2001-2019 O species, and the activated intermediates could be used for the substitutions with various nucleophilic reagents.7b,12 The conversions of P Created by potrace 1.16, written by Peter Selinger 2001-2019 O species to C(sp2)–P bonds are quite rare. Miura and coauthors have reported a Tf2O promoted activation of secondary phosphine oxides, which is applied for phosphination and intramolecular cyclization with alkynes.13 However, the scopes are limited with inner-alkynes. The application of H-phosphonates was not reported for the reaction (Chart 1).Herein we enclosed a novel Tf2O promoted reaction of terminal alkyne with H-phosphonates. Vinyl phosphonates were afforded under metal- and solvent-free conditions, in excellent Markovnikov-regio selectivity.Phenylacetylene (1a) was initially treated with diethyl phosphite (2a) in the presence of Tf2O in a molar ratio of 1 : 1 : 1. To our delight, diethyl 1-phenyl ethenylphosphonate (3aa), a Markovnikov addition product, was obtained in high regio-selectivity but in poor yield (10%). The reaction conditions were subsequently optimized with 1a and 2a. Considering Tf2O was moisture sensitive, all experiments were performed under nitrogen. Two equivalents 2a was used to ensure 1a was consumed as much as possible. The conversion and isolated yield were calculated based on 1a (
EntryMolar ratio of 1a/2a/CatBaseTemp.Solvent (1 mL)Conversion% (isolated yield%)b
11 : 2 : 1Rt12
21 : 2 : 140 °C46
31 : 2 : 160 °C92
41 : 2 : 165 °C98 (53)
51 : 2 : 180 °C98 (56)
61 : 2 : 0.565 °C79
71 : 2 : 0.865 °C92
81 : 2 : 1.265 °C86
91 : 2 : 165 °C0c
101 : 2 : 165 °CCH2Cl23
111 : 2 : 165 °CToluene9
121 : 2 : 165 °CTHF0
131 : 2 : 165 °CEtOAc22
141 : 2 : 1Na2CO365 °C0d
151 : 2 : 1Pyridine65 °C99 (64)d
161 : 2 : 12,6-Lutidine65 °C99 (54)d
171 : 2 : 1DBU65 °C99 (64)d
Open in a separate windowaReaction conditions: 1a (0.2 mmol), 2a (0.40 mmol) and Tf2O (0.2 mmol) stirring at different temperatures for 24 h.bThe conversions were estimated based on 1H NMR spectrum, and isolated yields were calculated based on 1a.cTfOH was used.d1.0 equiv. of base was used.When the mixture of 1a, 2a and Tf2O was stirred at room temperature, a new signal at 17.1 ppm was observed on 31P NMR spectrum. The two doublet peaks at 6.35 and 6.17 ppm on proton NMR spectrum, assigned as 3aa, was detected in 12% (entry 1 of 14 The conversion cannot be further improved at higher temperature such as 80 °C.When 0.5 equiv. Tf2O was used, the conversion of 1a was dropped to 79%. The usage of 0.8 equivalent of Tf2O led 92% conversion (entries 6 and 7). However, excessive Tf2O, such as 1.2 equivalents, resulted in the reduced conversion (86%, entry 8).Once triflic acid was used to replace Tf2O, 3aa was not detected (entry 9).To carry the reaction in some solvent such as dichloromethane, toluene, THF or ethyl acetate, gave worse result than neat condition (entries 10–13). In the presence of sodium carbonate, the reaction cannot take place (entry 14). The presence of pyridine, 2,6-lutidine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) slightly increased the conversion (entries 15–17).Adopting the above optimized condition, the reaction of alkyne with H-phosphonate was performed ( Open in a separate windowaIsolated yields based on 1a.Various terminal alkynes was then examined ( Open in a separate windowaIsolated yield.bTwo equivalents of Tf2O were used.cThe alkyne/P–H regent/Tf2O/pyridine were used in the molar ratio of 1 : 4 : 2 : 2.Some ethynyl heterocycles, such as 2- or 3-ethynylthiophene could be employed for the reaction, affording 3la or 3ma, respectively. For 1,4-diethynylbenzene (1n), the addition was realized when 2a and Tf2O were used in double equivalents. However, the alkynes having strong EWG, such as trifluoromethyl or 3-pyridinyl, cannot react with 2a. Aliphatic terminal alkynes, such as 1-octyne, also did not afford the product.The mechanism of the reaction was studied via in situ NMR experiments, and was proposed in Scheme 1. 2a and Tf2O formed triflate 4 of phosphite via an equilibrium.12b,15 Meanwhile, triflic acid was generated (step 1). The addition of triflic acid to 1a formed 1-phenylvinyl triflate 5 as an intermediate (step 2). The subsequent nucleophilic substitution of 5 with 4 formed vinyl phosphonate 3aa (step 3).Open in a separate windowScheme 1Proposed mechanism.The step 1 was confirmed by the observation of the signal of acidic proton in TfOH during the mixing of 2a with Tf2O (Fig. 1A). When 1a was added, 5 was detected, as seen the two doublet peaks at 5.61 and 5.38 ppm on 1H NMR spectrum (step 2 and Fig. 1B). When the mixture was heated at 60 °C, the signals of 3aa at 6.16–6.37 ppm emerged. The peaks were increased with prolonged heating, accompanied with the decreasing of the signals of 5 (step 3, Fig. 1C and D). Similar results were observed when Tf2O was initially mixed with 1a (Fig. 1E–H). After heating at 60 °C for 8 h, the signals of 1a, respected by the peak of terminal alkyne at 3.07 ppm, were disappeared (Fig. 1H).Open in a separate windowFig. 1The results of in situ NMR experiments of the reaction of 1a with 2a in the presence of triflic anhydride.The addition of triflic acid to 1a probably formed α-carbon ion as intermediate, which could be stabilized by phenyl and be converted to Markovnikov-product 5. Although the nucleophilic substitution on vinyl carbon was difficulty, the strong leaving activity of trifluoromethanesulfonyloxy on 5 enabled step 3 occurred. Miura proposed a cyclic phosphirenium intermediate for the addition and cyclization,13 which could be probably stabilized by the alkyl groups of inner-alkynes and secondary phosphine oxides. In our case, the electron-withdrawing alkoxyl on phosphorus of 2a was not favorable for the formation of the phosphirenium, thus the reaction proceeded via α-carbon ion and addition–substitution occurred.TfOH was necessary to the formation of 5 from 2a (step 2). However, triflic acid cannot sole promote the reaction, as seen in entry 9 of iii) species 4 by triflic anhydride, the lone electron pair on phosphorus of 4 could attack 5 to form the product. It was not sure the small quartet peak at 4.62 ppm belonged to 4 (Fig. 1F). On 31P NMR spectrum, the peak of 2a at 17.0 ppm obviously became broad in poor resolution when mixed with triflic anhydride (as seen in ESI). The results also supported the equilibrium between 2a and 4 (step 1).  相似文献   
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