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121.
Maja Stulemeijer Lieke W A M de Jong Theo J W Fiselier Sigrid W B Hoogveld Gijs Bleijenberg 《BMJ (Clinical research ed.)》2005,330(7481):14
Objective To evaluate the efficacy of cognitive behaviour therapy for adolescents aged 10-17 years with chronic fatigue syndrome.Design Randomised controlled trial.Setting Department of child psychology.Participants 71 consecutively referred patients with chronic fatigue syndrome; 36 were randomly assigned to immediate cognitive behaviour therapy and 35 to the waiting list for therapy.Intervention 10 sessions of therapy over five months. Treatment protocols depended on the type of activity pattern (relatively active or passive). All participants were assessed again after five months.Main outcome measures Fatigue severity (checklist individual strength), functional impairment (SF-36 physical functioning), and school attendance.Results 62 patients had complete data at five months (29 in the immediate therapy group and 33 on the waiting list). Patients in the therapy group reported significantly greater decrease in fatigue severity (difference in decrease on checklist individual strength was 14.5, 95% confidence interval 7.4 to 21.6) and functional impairment (difference in increase on SF-36 physical functioning was 17.3, 6.2 to 28.4) and their attendance at school increased significantly (difference in increase in percentage school attendance was 18.2, 0.8 to 35.5). They also reported a significant reduction in several accompanying symptoms. Self reported improvement was largest in the therapy group.Conclusion Cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome in adolescents. 相似文献
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123.
Bj?rnar Synstad Sigrid G?seidnes Daan M F Van Aalten Gert Vriend Jens E Nielsen Vincent G H Eijsink 《European journal of biochemistry》2004,271(2):253-262
Glycoside hydrolysis by retaining family 18 chitinases involves a catalytic acid (Glu) which is part of a conserved DXDXE sequence motif that spans strand four of a (betaalpha)8 barrel (TIM barrel) structure. These glycoside hydrolases are unusual in that the positive charge emerging on the anomeric carbon after departure of the leaving group is stabilized by the substrate itself (the N-acetyl group of the distorted -1 sugar), rather than by a carboxylate group on the enzyme. We have studied seven conserved residues in the catalytic center of chitinase B from Serratia marcescens. Putative roles for these residues are proposed on the basis of the observed mutational effects, the pH-dependency of these effects, pKa calculations and available structural information. The results indicate that the pKa of the catalytic acid (Glu144) is 'cycled' during catalysis as a consequence of substrate-binding and release and, possibly, by a back and forth movement of Asp142 between Asp140 and Glu144. Rotation of Asp142 towards Glu144 also contributes to an essential distortion of the N-acetyl group of the -1 sugar. Two other conserved residues (Tyr10 and Ser93) are important because they stabilize the charge on Asp140 while Asp142 points towards Glu144. Asp215, lying opposite Glu144 on the other side of the scissile glycosidic bond, contributes to catalysis by promoting distortion of the -1 sugar and by increasing the pKa of the catalytic acid. The hydroxyl group of Tyr214 makes a major contribution to the positioning of the N-acetyl group of the -1 sugar. Taken together, the results show that catalysis in family 18 chitinases depends on a relatively large number of (partly mobile) residues that interact with each other and the substrate. 相似文献
124.
Tight junctions are unique organelles in epithelial cells. They are localized to the apico-lateral region and essential for the epithelial cell transport functions. The paracellular transport process that occurs via tight junctions is extensively studied and is intricately regulated by various extracellular and intracellular signals. Fine regulation of this transport pathway is crucial for normal epithelial cell functions. Among factors that control tight junction permeability are ions and their transporters. However, this area of research is still in its infancy and much more needs to be learned about how these molecules regulate tight junction structure and functions. In this review we have attempted to compile literature on ion transporters and channels involved in the regulation of tight junctions. 相似文献
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126.
A mammary gland EST showing linkage disequilibrium to a milk production QTL on bovine Chromosome 14 总被引:10,自引:0,他引:10
Christian Looft Norbert Reinsch Christina Karall-Albrecht Sven Paul Maren Brink Hauke Thomsen Gudrun Brockmann Christa Kühn Manfred Schwerin Ernst Kalm 《Mammalian genome》2001,12(8):646-650
As part of a genome scan, ESTs derived from mammary gland tissue of a lactating cow were used as candidate genes for quantitative
trait loci (QTL), affecting milk production traits. Resource families were genotyped with 247 microsatellite markers and 4
polymorphic ESTs. It was shown by linkage analysis that one of these ESTs, KIEL_E8, mapped to the centromeric region of bovine
Chromosome (Chr) 14. Regression analysis revealed the presence of a QTL, with significant effect on milk production, in this
chromosome region, and analysis of variance showed no significant interaction of marker genotype and family. The estimated
significant differences between homozygous marker genotypes were 140 kg milk, −5.02 kg fat yield, and 2.58 kg protein yield
for the first 100 days of lactation. Thus, there was strong evidence for a complete or nearly complete linkage disequilibrium
between KIEL_E8 and the QTL. To identify the biological function of KIEL_E8, we extended the sequence for 869 bp by 5′-RACE.
A 560-bp fragment of this shows a 90.9% similarity to a gene encoding a cysteine- and histidine-rich cytoplasmic protein in
mouse. Although such a protein may have a regulatory function for lactation and a linkage disequilibrium between the EST marker
and the QTL has been observed, it remains to be elucidated whether they are identical or not. Nevertheless, KIEL_E8 will be
an efficient marker to perform marker-assisted selection in the Holstein-Friesian population.
Received 20 October 2000 / Accepted: 11 April 2001 相似文献
127.
Gro O. Nygaard Elisabeth G. Celius Sigrid A. de Rodez Benavent Piotr Sowa Marte W. Gustavsen Anders M. Fjell Nils I. Landr? Kristine B. Walhovd Hanne F. Harbo 《PloS one》2015,10(8)
New treatment options may make “no evidence of disease activity” (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to “evidence of disease activity” (EDA) with at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one-year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8–2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0–1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity. 相似文献
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129.
The effects of various concentrations of urea and guanidine hydrochloride on enzyme activity and on subunit association were determined. Incubation of thymidylate synthetase with buffered solutions of 3M to 3.5M guanidine hydrochloride or 5 M to 6 M urea resulted in the loss of about 90% of the enzyme activity. Under these denaturing conditions a red shift of the fluorescence emission maximum from 340 nm to 351 nm was observed together with a significant decrease in the relative fluorescence intensity of the protein. Studies at both 4 degrees C and 25 degrees C indicated that the enzyme was in the dimer form in 2 M guanidine hydrochloride but was dissociated into monomers in concentrations of this denaturant of 3 M and above. Although only monomeric species were evident at 4 degrees C in 6 M urea, at 25 25 degrees C this denaturant caused protein aggregation which increased with decreasing phosphate buffer concentration. Enzyme (5 mg/ml) in 0.5 M potassium phosphate buffer, pH 6.8, containing 4 M guanidine hydrochloride gave a minimum S20, w value of 1.22S at 25 degrees C. Sedimentation behavior of the native enzyme in the range of 5 to 20 mg/ml was only slightly concentration-dependent (4.28 S to 4.86 S) but extensive aggregation occurred above 20 mg/ml. 相似文献
130.
Anti-metabolites, such as methotrexate, 5-fluoropyrimidines or hydroxyurea, induced progressive formation of DNA lesions. 5-Fluoropyrimidines induce DNA lesions either by incorporation of the drug into DNA or by a mechanism not involving incorporation. The second mechanism, not involving incorporation, is also seen with methotrexate and hydroxyurea. The three anti-metabolites have in common their ability to reduce intracellular levels of nucleotides, resulting in reduced efficiency of repair of DNA lesions. The lesions probably appear spontaneously, independently of the drug treatment. 相似文献