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71.
Unsöld B Kerst G Brousos H Hübner M Schreiber R Nitschke R Greger R Bleich M 《Pflügers Archiv : European journal of physiology》2000,441(2-3):368-378
Previous studies have shown that heteromultimeric KCNQ1/KCNE1 (KvLQT1/minK) channels and homomultimeric KCNQ1 (KvLQT1) channels exhibit different current properties, e.g. distinct kinetics and different sensitivities to drugs. In this study we report on the divergent responses to internal pH changes and further characterize some of the current properties of the human isoforms of KCNQ1 and KCNE1 expressed in Chinese hamster ovary (CHO) cells or Xenopus laevis oocytes. Decreasing the bath temperature from 37 degrees C to 20 degrees C increased the half-activation time by a factor of 5 for KCNQ1/KCNE1 currents (IKs) but by only twofold (not significant) for KCNQ1 currents (IK) in CHO cells. Acidification of cytosolic pH (pHi) increased IKs but decreased 1K whereas intracellular alkalinization decreased I(Ks) but increased IK. pHi-induced changes in intracellular Ca2+ activity ([Ca2+]i) did not correlate with the current responses. At 20 degrees C mefenamic acid (0.1 mM) significantly augmented IKs but slightly decreased IK. It changed the slow activation kinetics of I(Ks) to an instantaneous onset. The form of the current/voltage (I/V) curve changed from sigmoidal to almost linear. In contrast, at 37 degrees C, mefenamic acid also increased I(Ks) but slowed the activation kinetics and shifted the voltage activation to more hyperpolarized values without markedly affecting the sigmoidal shape of the I/V curve. The potassium channel blockers clotrimazole and tetrapentylammonium (TPeA) inhibited I(Ks) with a lower potency than I(K). These results show that coexpression of KCNE1 reversed pH regulation of KCNQ1 from inhibition to activation by acidic pHi. In addition, KCNE1 altered the pharmacological properties and sensitivity to temperature of KCNQ1. The pH-dependence of I(Ks) might be of clinical and pathophysiological relevance in the pathogenesis of ischaemic cardiac arrhythmias. 相似文献
72.
Paul J Martin George B McDonald Jean E Sanders Claudio Anasetti Frederick R Appelbaum H Joachim Deeg Richard A Nash Effie W Petersdorf John A Hansen Rainer Storb 《Biology of blood and marrow transplantation》2004,10(5):320-327
The reported incidence of grades II to IV acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation with HLA-identical sibling donors has increased considerably during the past 15 to 20 years at our center. The purpose of this study was to evaluate the potential reasons for this change. We reviewed organ stages and overall grades of GVHD for 2220 patients who received a first marrow or peripheral blood cell transplant from an HLA-identical sibling or an HLA-allele-matched unrelated donor with the use of a posttransplantation immunosuppressive regimen that included both methotrexate and cyclosporine between 1985 and 2001. The most striking change was an increased incidence of stage 1 gut involvement from 10% to 20% before 1992 to 50% to 60% since 1992, both with related and unrelated donors. This change increased the incidence of grade II GVHD with sibling donors, such that the overall incidence of grade II to IV GVHD is now 60% to 70%. Among patients with chronic myeloid leukemia in chronic phase, the increasingly frequent diagnosis of acute GVHD since 1992 has not been associated with decreased survival. A high diagnostic sensitivity and increased awareness that gut GVHD can occur without skin involvement account for the increased incidence of acute GVHD at our center. 相似文献
73.
Alexander Rodewald Rainer Pankau Angela Gosch Armin Wessel 《American journal of medical genetics. Part A》1994,53(3):227-235
The dermatoglyphic patterns of fingertips and palms of 115 patients with Williams-Beuren syndrome (WBS) were analysed and compared with the data from 199 control individuals from Germany. The following combination of dermatoglyphic patterns appears to be characteristic to WBS: an excess of whorls on all fingertips; high termination values of the main lines D, B, and A; frequent absence of C triradius (C°); high frequencies of ulnar loops on the hypothenar and distal loops on the 2nd, 3rd, and 4th inter digital areas, of distal axial triradii t", and of abnormal palmar creases such as simian crease and Sydney lines. The combination of fingertip and palmar patterns expressed by a “Log.Score-Index,” provides a high degree of discrimination between the WBS patients (92%) and the control group (88%). A “phantom picture” for WBS was constructed, which can be used for its diagnosis. © 1994 Wiley-Liss, Inc. 相似文献
74.
In addition to their robust difference in trait anxiety, as illustrated by a variety of behavioral tests, HAB and LAB rats differ in their stress coping strategies, the former being more susceptible and vulnerable to stressor exposure and preferring more passive strategies. HAB rats of either gender show signs of a hyper-reactive hypothalamic-pituitary-adrenocortical (HPA) axis, thus resembling psychiatric patients. As shown by in situ hybridization and microdialysis in freely behaving animals, both the expression and release of vasopressin in the hypothalamic paraventricular nucleus are higher in HAB than in LAB rats, thus contributing to the HPA axis hyperdrive. Accordingly, in HAB animals, administration of a V1 receptor antagonist normalized the pathological outcome of the dexamethasone/corticotropin-releasing hormone test and triggered behavioral changes toward reduced anxiety and active stress coping. Pharmacological validation has revealed signs of depressive-like behavior, as HAB but not LAB rats have shown more active stress coping behavior and a normalized HPA axis after treatment with paroxetine. Of interest, this antidepressant reduced the hypothalamic overexpression of vasopressin; this novel mechanism of action is likely to contribute to paroxetine effects on both behavioral and neuroendocrine parameters. Cross-mating and cross-fostering paradigms showed that the divergent emotionality in HAB vs. LAB rats is determined genetically, rather than postnatally through maternal behavior. As the behavioral and neuroendocrine phenotyping pointed to the vasopressin gene as a candidate gene critically involved in anxiety, preliminary genetic approaches have been focused on this gene, revealing single nucleotide polymorphisms (SNPs) in the promotor area of the vasopressin gene in HAB, but not LAB rats. HAB/LAB rats are thus proving to be a unique animal model to identify and characterize neurobiological, neuroendocrine, and genetic correlates of trait anxiety, and perhaps depression, in humans. 相似文献
75.
76.
The swelling behaviour, the time-dependence of the uptake of Cu2+-ions, and the pH-dependence of the uptake of Cu2+-, Ni2+-, Cd2+-, Zn2+- and Mg2+-ions of crosslinked poly[1-(4,5-dicarboxy-1-imidiazolyl)ethylene] ( 1 ) and poly{1-[p-(4,5-dicarboxy-2-imidazolyl)phenyl]ethylene} ( 2 ) were investigated. Both resins have a high selectivity for heavy metal ions. For resins 1 the uptake of heavy metal ions in the presence of an excess of EDTA was studied. Furthermore the possibility to remove Hg2+-ions from aqueous alkalichloride solutions by resin 1 was investigated. 相似文献
77.
Thomas C. Klein Rainer Dffinger Mark B. Pepys Ulrich Rüther Bruno Kyewski 《European journal of immunology》1995,25(12):3489-3495
The understanding of immunological tolerance has been greatly aided by the development of transgenic animal models in which expression of a specific T cell receptor (or B cell receptor) and its cognate self antigen is experimentally controlled. In most cases, expression of the self antigen was constitutive and did not allow for variation of its time- and dose-dependent expression pattern, parameters which are known to influence the balance of tolerance versus immunity. We describe a transgenic model in which expression of human C-reactive protein (hCRP), an acute-phase protein, is tightly controlled at basal levels (female mice express around 10?9 M and male mice 5 × 10?7 M circulating hCRP) and is highly inducible (induction factor of 25–500). T cells from C57BL/6 mice recognize two epitopes of hCRP termed A (residues 79–95) and B (residues 87–102). Different efficacies of presentation in vitro and in vivo identify epitope A as subdominant and epitope B as dominant. T cells of non-induced hCRP transgenic mice are tolerant to the dominant epitope, but reactive to the subdominant epitope. A hCRP-specific IgG antibody response is detectable in transgenic mice, but is weaker than in littermates. Upon induction of hCRP, both T cell epitopes are presented by thymic and splenic antigen-presenting cells (APC) in vivo. Kinetics of presentation by splenic APC closely match serum kinetics of hCRP, whereas presentation in the thymus is considerably prolonged. This model enables epitope-specific T cell tolerance to be studied as a function of time- and dose-dependent expression of the self antigen. 相似文献
78.
Oskar Nuyken Günter Lattermann Wolfgang Dannhorn Rainer Vogel 《Macromolecular chemistry and physics.》1992,193(5):1057-1069
Poly(epichlorohydrin) and poly(epichlorohydrin-co-ethylene oxide) were modified by reaction with potassium thiocyanate (KSCN), tetrabutylammonium p-toluenesulfinate (NBu4SO2C7H7) and tetrabutylammonium benzenesulfinate (NBu4SO2C6H5). Though the substitution of chlorine in the polymers with these nucleophilic reagents in most cases is accompanied by side reactions, appropriate reaction conditions allow degrees of substitution higher than 90% to be obtained. The glass transition temperature (Tg) of the thiocyanate-modified homo- and copolymer exhibits only a small increase with increasing degree of substitution. While the Tg of the original homo- and copolymer is observed at ?20°C and ?38°C, respectively, the glass transition of the highly substituted homopolymer occurs at ?12°C and for the copolymer at ?31°C. On the other hand, the thiocyanate-modified polymers show a remarkably higher decomposition temperature of about 250°C as compared with that of the unmodified polymers (160–180°C). In addition, the solubility is markedly influenced by the substitution. While the original homo- and copolymers are soluble in, e.g., benzene and toluene, the highly modified products are only soluble in polar solvents such as THF, acetone, DMSO and diglyme. Introducing sulfonyl groups, the resulting polymers exhibit a glass transition temperature increased to a greater extent. For the homopolymer with the highest degree of substitution (98,3%), a Tg of 73°C is observed. Concerning the decomposition temperature, a drastical increase up to 370°C occurs. Finally the influence of phase transfer catalysts on the described reactions was investigated. 相似文献
79.
Rainer Burghard Ralf Pallacks Nader Gordjani Jekabs U. Leititis Bernhard J. Hackelöer Matthias Brandis 《Pediatric nephrology (Berlin, Germany)》1987,1(4):574-580
Protein content and protein composition were studied in amniotic fluid obtained from 171 healthy pregnant women between the 16th and 38th week of gestation, using microgradient gel electrophoresis to separate proteins according to their molecular size into albumin (68 KD), proteins of low molecular weight (LMW proteins, <68 KD), and proteins of high molecular weight (HMW proteins, >68 KD). Additionally -1-microglobulin (-1-MG, 33 KD) and -2-microglobulin (-2-MG, 11,8 KD) were analysed as micromolecular marker proteins. Concentrations of LMW proteins were 0.15–0.22 g/l, of -1-MG 28.4–34.5 mg/l, and of -2-MG 7.2–11.6 mg/l during the second trimester of gestation, and thereafter decreased progressively to 0.03 g/l, 14.1 mg/l and 2.4 mg/l respectively near term. The same developmental trends were confirmed by calculating the protein/creatinine ratios in amniotic fluid. The concentrations of LMW proteins found in the first postnatal urine of 73 healthy infants born prematurely or at term were similar to those in amniotic fluid of corresponding fetal age. Concentrations of albumin and HMW proteins in postnatal urine were about 5% and 15% respectively when compared with amniotic fluid concentrations. No strong correlation existed between gestational age and either of the analysed proteins which would allow accurate assessment of fetal maturation by protein analysis in amniotic fluid. It is concluded that fetal urinary excretion is the major determinant of the microprotein content of amniotic fluid. Microproteins seem to reflect an increasing tubular reabsorption capacity, which accelerates rapidly after the second trimester of gestation. 相似文献
80.
Paolo Santicioli Rainer Gamse Carlo Alberto Maggi Alberto Meli 《Naunyn-Schmiedeberg's archives of pharmacology》1987,335(5):580-587
Summary 1. The effect of streptozotocin (STZ) induced diabetes on rat urinary bladder function was investigated by means of in vivo cystometry and in vitro recording of bladder strips contractility. A group of sucrose-fed animals was included to determine to what extent the STZ-induced changes were ascribable to the increased diuresis. 2. After 7–9 weeks from STZ injection there was a marked increase in weight of bladder and ureters. Cystometry revealed a marked increase in bladder capacity (volume threshold) although pressure threshold and amplitude of micturition contraction were unaffected. Sucrose-fed animals, having normal blood glucose levels but a similar increase in urine production exhibited cystometric changes identical to those of STZ animals. 3. In vitro experiments indicated that the response to field stimulation (0.1–20 Hz) is reduced in STZ-pretreated but increased in sucrose-fed animals, as compared to controls. 4. The content of urinary bladder and ureters in sensory neuropeptides (substance-P, neurokinin-A and calcitonin-gene related peptide-like immunoreactivity) was increased by STZ diabetes when values were corrected for the increased weight of these organs. 5. The capsaicin-induced contraction of the rat isolated bladder strips, presumably caused by neuropeptides released from intramural sensory nerves, is unaffected by STZ diabetes. 6. These findings indicate that STZ diabetes produces, at an early stage, changes similar to those reported to occur in the human disease, e. g. a greater bladder capacity with unimpaired voiding function. The increased bladder capacity of STZ-rats seems largely, if not solely, ascribable to changes in physical properties of the detrusor muscle, thereby allowing accomodation of greater than normal volumes with similar increase of intraluminal pressure. No sign of diabetic neuropathy of the capsaicin-sensitive sensory nerves can be observed at this stage (7–9 weeks) of STZ diabetes.
Send offprint requests to P. Santicioli at the above address 相似文献