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81.
目的观察定量毛细管速率法测定的红细胞沉降率(ESR)与红细胞压积(HCT)的相关关系,以确定其是否需要在实验前对HCT进行处理,并确定其测定结果是否需要进行校正。方法随机抽取广州市第一人民医院和广州市胸科医院住院病人标本120例(男64例,女56例),健康体检者标本100例(男50例,女50例),均采用EDTA-K_2抗凝,分别运用以定量毛细管速率法的Microtest1自动血沉仪测定ESR,用KX-21血细胞分析仪测定HCT,对数据进行直线相关分析。结果Microtest1自动血沉仪测得的健康体检男性组ESR与其HCT相关系数r=-0.257,P=0.073;女性组相关系数r=-0.209,P=0.146。病例男性组ESR与其HCT相关系数r=-0.122,P=0.376;女性组相关系数r=-0.139,P=0.342。结论定量毛细管速率法测定的ESR与HCT间,无论是病例组还是健康组,均不存在直线相关关系。采用此法测定的ESR无需调整标本的HCT,测得的ESR也无需经HCT值校正。 相似文献
82.
Dietary resistant starch and chronic inflammatory bowel diseases 总被引:5,自引:0,他引:5
Jacobasch G Schmiedl D Kruschewski M Schmehl K 《International journal of colorectal disease》1999,14(4-5):201-211
These studies were performed to test the benefit of resistant starch on ulcerative colitis via prebiotic and butyrate effects.
Butyrate, propionate, and acetate are produced in the colon of mammals as a result of microbial fermentation of resistant
starch and other dietary fibers. Butyrate plays an important role in the colonic mucosal growth and epithelial proliferation.
A reduction in the colonic butyrate level induces chronic mucosal atrophy. Short-chain fatty acid enemas increase mucosal
generation, crypt length, and DNA content of the colonocytes. They also ameliorate symptoms of ulcerative colitis in human
patients and rats injected with trinitrobenzene sulfonic acid (TNBS). Butyrate, and also to a lesser degree propionate, are
substrates for the aerobic energy metabolism, and trophic factors of the colonocytes. Adverse butyrate effects occur in normal
and neoplastic colonic cells. In normal cells, butyrate induces proliferation at the crypt base, while inhibiting proliferation
at the crypt surface. In neoplastic cells, butyrate inhibits DNA synthesis and arrests cell growth in the G1 phase of the
cell cycle. The improvement of the TNBS-induced colonic inflammation occurred earlier in the resistant starch (RS)-fed rats
than in the RS-free group. This benefit coincided with activation of colonic epithelial cell proliferation and the subsequent
restoration of apoptosis. The noncollagenous basement membrane protein laminin was regenerated initially in the RS-fed group,
demonstrating what could be a considered lower damage to the intestinal barrier function. The calculation of intestinal short-chain
fatty acid absorption confirmed this conclusion. The uptake of short-chain fatty acids in the colon is strongly inhibited
in the RS-free group, but only slightly reduced in the animals fed with RS. Additionally, RS enhanced the growth of intestinal
bacteria assumed to promote health. Further studies involving patients suffering from ulcerative colitis are necessary to
determine the importance of RS in the therapy of a number of intestinal diseases and the maintenance of health.
Accepted: 11 August 1999 相似文献
83.
研究龙马酶(EC 3. 1. 1. 3)固定化载体、固定化条件和固定化酶的性质。方法:固定化采用吸附法。结果:固定化最适条件:酶液PH9.0,吸附时间1.5 h,酶浓度1.5 g/100 ml,在此条件下固定化酶活力53 u/g载体,活力回收率71%。固定化酶的最适作用温度和pH较游离酶高,范围较游离酶广,耐热性、酸碱稳定性比游离酶好。结论:固定化酶性能比游离酶得到提高。 相似文献
84.
Fattinger K Benowitz NL Jones RT Verotta D 《European journal of clinical pharmacology》2000,56(4):305-310
Objective: Several xenobiotics, including cocaine, are dosed by the nasal route for systemic effects. The aim of this study was to
estimate and compare cocaine input into the systemic circulation after oral and nasal dosing, and to determine the relevance
of local absorption through the nasal mucosa.
Methods: Cocaine was administered to healthy volunteers through the intravenous, oral, and nasal routes. Cocaine serum concentrations
were measured at frequent intervals. From these data, the gastrointestinal, nasal, and nasal mucosa input rate functions were
determined using nonparametric, subject-specific population deconvolution.
Results: After oral dosing, cocaine input into systemic circulation increased slowly and peaked around 45 min after ingestion. The
median systemic bioavailability after oral dosing was 33%. After nasal dosing, drug input was substantial even during the
first minute and showed two peaks at 10 min and 45 min after ingestion. Since the second peak after nasal dosing closely resembled
drug input after oral administration, we hypothesized that, after nasal administration, a part of the dose is swallowed and
thereafter absorbed gastrointestinally. The data from the sessions with nasal cocaine administration were reanalyzed assuming
the same shape for gastrointestinal drug input as after oral dosing. The fraction absorbed through the nasal mucosa was estimated
to be 19% (95% CI: 11–26%). The fraction absorbed through the nasal mucosa contributed 31% (95% CI: 23–37%) of total systemic
cocaine exposure.
Conclusions: Our data suggest that the main reason addicts prefer nasal to oral cocaine dosing is faster absorption, enhancing the subjective
effects rather than higher bioavailability.
Received: 28 December 1999 / Accepted in revised form: 23 March 2000 相似文献
85.
Zusammenfassung Ausgehend von der Ähnlichkeit der Transportsysteme für Aminosäuren in Niere und Darm wurde die Frage untersucht, ob bei Rachitis mit Hyperaminoacidurie auch der Aminosäurentransport im Dünndarm gestört ist. In umgestülpten Darmsäckchen wurde die Absorption von 14C-markierten Aminosäuren bei 2 Ferkeln mit erblicher Pseudomangelrachitis und 7 klinisch gesunden Tieren gemessen. Die Versuche ergaben, daß bei bestehender aktiver Rachitis mit Hyperaminoacidurie die intestinale Aminosäurenabsorption nicht beeinträchtigt ist. Die Absorption nahm dagegen mit dem Alter der Versuchstiere signifikant ab. Das isolierte Auftreten eines Transportschadens für Aminosäuren in der Niere läßt den Schluß zu, daß dieser Defekt nicht durch direkte Einwirkung hämatogener Faktoren (erhöhter PTH-Spiegel oder Mangel an Vitamin D-Metaboliten) auf die Transportsysteme hervorgerufen wird, sondern die Folge vorgeschalteter spezifischer Effekte auf die Tubulusepithelien darstellt.
Intestinal amino acid absorption in vitamin D dependent rickets
Since structure and specifity of amino acid transport systems are basically similar in kidney and intestines it was suspected that rickets associated with hyperaminoaciduria was linked with defective intestinal amino acid uptake. Therefore amino acid absorption from everted sacs of small intestines was studied in 2 piglets suffering from vitamin D dependent rickets, and 7 healthy piglets using 14C labelled amino acids. The experiments revealed an unaffected intestinal absorption in the rachitic animals, whereas the uptake decreased significantly with increasing age of the experimental animals. The results from these studies suggest that regulatory factors in the blood system, e. g. increased level of PTH or lack of specific vitamin D metabolites, do not directly affect amino acid transport systems in kidney and intestines. It is concluded that hyperaminoaciduria has to be mediated through specific and thus far unidentified effects at the tubular cell level.
Im Rahmen des Sonderforschungsbereichs 146 Versuchstierforschung finanziell gefördert. 相似文献
86.
Shibin Mathew David Tess Woodrow Burchett George Chang Nathaniel Woody Christopher Keefer Christine Orozco Jian Lin Samantha Jordan Shinji Yamazaki Rhys Jones Li Di 《Journal of pharmaceutical sciences》2021,110(4):1799-1823
Volume of distribution at steady state (Vss) is an important pharmacokinetic parameter of a drug candidate. In this study, Vss prediction accuracy was evaluated by using: (1) seven methods for rat with 56 compounds, (2) four methods for human with 1276 compounds, and (3) four in vivo methods and three Kp (partition coefficient) scalar methods from scaling of three preclinical species with 125 compounds. The results showed that the global QSAR models outperformed the PBPK methods. Tissue fraction unbound (fu,t) method with adipose and muscle also provided high Vss prediction accuracy. Overall, the high performing methods for human Vss prediction are the global QSAR models, Øie-Tozer and equivalency methods from scaling of preclinical species, as well as PBPK methods with Kp scalar from preclinical species. Certain input parameter ranges rendered PBPK models inaccurate due to mass balance issues. These were addressed using appropriate theoretical limit checks. Prediction accuracy of tissue Kp were also examined. The fu,t method predicted Kp values more accurately than the PBPK methods for adipose, heart and muscle. All the methods overpredicted brain Kp and underpredicted liver Kp due to transporter effects. Successful Vss prediction involves strategic integration of in silico, in vitro and in vivo approaches. 相似文献
87.
以水溶性α.β.γ.δ—四—(4—三甲铵苯基)卟啉[T-(4-TAP)P]作显色剂,测定了食品中的痕量铜。对实验条件及共存离子的干扰进行了探讨。在乙醇介质及强酸条件下测定时,其选择性及灵敏度均有显著提高。摩尔吸收系数为4.5×10~5 1mol~(-1).cm~(-1)最小检验量为:0.14ng/cm~2,回收率为96.2~106%,变异系数为:0.46~3.6%。操作简便,结果满意。 相似文献
88.
J. W. Wiechers 《Pharmacy World & Science》1989,11(6):185-198
There is currently a high level of interest in using the skin as a route for delivering drugs. The skin, however, provides an efficient barrier against percutaneous absorption of drugs. This barrier function can be ascribed to the macroscopical structure of the stratum corneum, which consists of alternating lipoidal and hydrophylic regions. For this reason, physico-chemical characteristics of the drug, such as partition coefficient and molecular weight, play an important role in determining the facility of percutaneous absorption. Another factor to consider in transdermal drug delivery, is the vehicle in which the drug is formulated as it acts on the release of drug from the formulation. Moreover, vehicles may also interact with human stratum corneum, thereby affecting its barrier function. Surfactants and penetration enhancers are well-known examples of the latter. Subsequently, dosing conditions, such as humidity, temperature and occlusion, also have their impact on the actual input (rate) of drug through human skin. Finally, all bits of information are combined to form a reasonably faithful picture of percutaneous absorption. 相似文献
89.
Alex Avdeef Melissa Strafford Eric Block Michael P. Balogh Walter Chambliss Ikhlas Khan 《European journal of pharmaceutical sciences》2001,14(4):271-280
The assessment of transport properties of 23 drug and natural product molecules was made using the in vitro model based on filter-immobilized artificial membranes (filter-IAM), assembled from phosphatidylcholine in dodecane, in buffer solutions at pH 7.4. Five of the compounds were lactones extracted from the roots of the kava-kava plant. Experiments were designed to test the effects of stirring (0–600 rpm) during assays and the effects of varying the assay times (2–15 h). The highly mobile kava lactones permeated in the order dihydromethisticin (40)>yangonin (37)>kavain (34)>methisticin (32)>desmethoxyyangonin (26), the numbers in parentheses being the measured effective permeabilities in units of 10−6 cm/s. By comparison, commercial drugs ranked: phenazopyridine (35)>testosterone (19)>propranolol (13)>ketoconazole (6.3)>piroxicam (2.2)>caffeine (1.7)>metoprolol (0.8)>terbutaline (0.01). In addition to permeability measurements, membrane retention of compounds was determined. Yangonin, desmethoxyyangonin, ketoconazole, and phenazopyridine were more than 60% retained by the artificial membranes containing phospholipids. Stirring during assay significantly increased the observed permeabilities for highly mobile molecules, but had minimal impact on the poorly permeable molecules. The influence of hydrogen bonding was explored by determining permeabilities using filters coated with dodecane free of phospholipids. In the filter-IAM method, concentrations were determined by microtitre plate UV spectrophotometry and by LC–MS. Higher-throughput was achieved with direct UV by the use of 96-well microtitre plate formats and with LC–MS by the use of cassette dosing (five-in-one). 相似文献
90.
中枢性作用的抗高血压药盐酸可乐定、其透皮吸收制剂称为乐百事膏,用家兔体外剩余法预测其吸收率,贴药后3小时透皮吸收累计约18%、12小时约39.7%、24小时约52.79%,贴药3天后累积吸收约60.7%。由于可乐定用药量小,有效血药浓度极低,须用较精密的分析手段才能准确测出血药浓度,应用体外剩余法可间接了解透皮吸收情况。经实验证明不失为一简单而有效的方法,具有一定的参考价值。 相似文献