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991.
Matthias Griese Robert Essl Reinhold Schmidt Manfred Ballmann Karl Paul Ernst Rietschel Felix Ratjen the Beat Study Group 《Respiratory research》2005,6(1):133
Background
In a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time.Methods
As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV1 94% of predicted) at three times over a three year period.Results
There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV1, MEF75/25%VC, and MEF25%VC. The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period.Conclusion
Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease. 相似文献992.
Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor receptor downregulation 总被引:2,自引:0,他引:2
The ubiquitin ligase Cbl mediates ubiquitination of activated receptor tyrosine kinases (RTKs) and interacts with endocytic scaffold complexes, including CIN85/endophilins, to facilitate RTK endocytosis and degradation. Several mechanisms regulate the functions of Cbl to ensure the fine-tuning of RTK signalling and cellular homeostasis. One regulatory mechanism involves the binding of Cbl to Sprouty2, which sequesters Cbl away from activated epidermal growth factor receptors (EGFRs). Here, we show that Sprouty2 associates with CIN85 and acts at the interface between Cbl and CIN85 to inhibit EGFR downregulation. The CIN85 SH3 domains A and C bind specifically to proline-arginine motifs present in Sprouty2. Intact association between Sprouty2, Cbl and CIN85 is required for inhibition of EGFR endocytosis as well as EGF-induced differentiation of PC12 cells. Moreover, Sprouty4, which lacks CIN85-binding sites, does not inhibit EGFR downregulation, providing a molecular explanation for functional differences between Sprouty isoforms. Sprouty2 therefore acts as an inducible inhibitor of EGFR downregulation by targeting both the Cbl and CIN85 pathways. 相似文献
993.
Neuberger MS Di Noia JM Beale RC Williams GT Yang Z Rada C 《Nature reviews. Immunology》2005,5(2):171-178
Somatic hypermutation of immunoglobulin genes occurs at both C.G pairs and A.T pairs. Mutations at C.G pairs are created by activation-induced deaminase (AID)-catalysed deamination of C residues to U residues. Mutations at A.T pairs are probably produced during patch repair of the AID-generated U.G lesion, but they occur through an unknown mechanism. Here, we compare the popular suggestion of nucleotide mispairing through polymerase error with an alternative possibility, mutation through incorporation of dUTP (or another non-canonical nucleotide). 相似文献
994.
Mohammad?E?ParsanezhadEmail author Saeed?Alborzi Jaleh?Zolghadril Maryam?Parsa-Nezhad Gholamreza?Keshavarzi Gholamhossein?R?Omrani Ernst?H?Schmidt 《Reproductive biology and endocrinology : RB&E》2005,3(1):31
Background
The effects of ovarian drilling on the serum levels of gonadotropins and androgens have been studied previously. The aim of this study is to evaluate the effects of ovarian drilling on the serum prolactin levels and its relation to ovulation in women with polycystic ovary syndrome. 相似文献995.
The purpose of this research was to evaluate the influence of dry granulation parameters on granule and tablet properties
of spray-dried extract (SDE) fromMaytenus ilicifolia, which is widely used in Brazil in the treatment of gastric disorders. The compressional behavior of the SDE and granules
of the SDE was characterized by Heckel plots. The tablet properties of powders, granules, and formulations containing a high
extract dose were compared. The SDE was blended with 2% magnesium stearate and 1% colloidal silicon dioxide and compacted
to produce granules after slugging or roll compaction. The influences of the granulation process and the roll compaction force
on the technological properties of the granules were studied. The flowability and density of spray-dried particles were improved
after granulation. Tablets produced by direct compression of granules showed lower crushing strength than the ones obtained
from nongranulated material. The compressional analysis by Heckel plots revealed that the SDE undergoes plastic deformation
with a very low tendency to rearrangement at an early stage of compression. On the other hand, the granules showed an intensive
rearrangement as a consequence of fragmentation and rebounding. However, when the compaction pressure was increased, the granules
showed plastic deformation. The mean yield pressure values showed that both granulation techniques and the roll compaction
force were able to reduce the material's ability to undergo plastic deformation. Finally, the tablet containing a high dose
of granules showed a close dependence between crushing strength and the densification degree of the granules (ie, roll compaction
force).
Published: October 14, 2005 相似文献
996.
Bohnstedt KC Karlberg B Basun H Schmidt S 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,827(1):39-43
F2-isoprostanes are produced by the non-enzymatic peroxidation of arachidonic acid in membrane phospholipids. This paper describes a new method for the determination of all four classes of F2-isoprostanes in human cerebrospinal fluid (CSF) involving separation on a 1 mm x 150 mm porous graphitic carbon (PGC) column and detection by triple quadrupole mass spectrometry in negative-ion electrospray mode. The sample pre-treatment consisted of an ultrafiltration step, following which 300 microl of CSF sample could be injected directly onto a 1 mm x 10 mm PGC guard column functioning as a trap for the analytes. The loading solvent was Milli-Q water at 125 microl/min. After 3 min, the sample was switched into the separation column. The F2-isoprostanes were separated in 20 min using a linear solvent gradient comprising water, methanol, acetonitrile and ammonium hydroxide at a pH of 9.5 and a flow of 50 microl/min The limit of detection (calculated as 3S/N) was approximately 40 pM (14 pg/ml). The assay was linear within the examined range (18-450 pg/ml), using CSF spiked with iPF2alpha-III standard (r(2)>0.995). Repeatability data were calculated for CSF spiked to 90 pg/ml and the relative standard deviation (RSD) obtained was 3% (n=6). 相似文献
997.
Preparative parallel protein purification (P4) 总被引:1,自引:0,他引:1
Strömberg P Rotticci-Mulder J Björnestedt R Schmidt SR 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,818(1):11-18
In state of the art drug discovery, it is essential to gain structural information of pharmacologically relevant proteins. Increasing the output of novel protein structures requires improved preparative methods for high throughput (HT) protein purification. Currently, most HT platforms are limited to small-scale and available technology for increasing throughput at larger scales is scarce. We have adapted a 10-channel parallel flash chromatography system for protein purification applications. The system enables us to perform 10 different purifications in parallel with individual gradients and UV monitoring. Typical protein purification applications were set up. Methods for ion exchange chromatography were developed for different sample proteins and columns. Affinity chromatography was optimized for His-tagged proteins using metal chelating media and buffer exchange by gel filtration was also tested. The results from the present system were comparable, with respect to resolution and reproducibility, with those from control experiments on an AKTA purifier system. Finally, lysates from 10 E. coli cultures expressing different His-tagged proteins were subjected to a three-step parallel purification procedure, combining the above-mentioned procedures. Nine proteins were successfully purified whereas one failed probably due to lack of expression. 相似文献
998.
Mao Y Lai C Vogtentanz G Schmidt B Day T Miller J Brandon DL Chen D 《The protein journal》2005,24(5):275-282
Monoclonal antibodies against soybean Bowman-Birk protease inhibitor (BBI) have been generated and used to detect and quantify
BBI in foods, soybean germplasm, and animal tissues and fluids. The purpose of this study was to determine the recognition
sites of two monoclonal antibodies to BBI (mAb 238 and mAb 217) in relation to the protease-inhibitory sites of BBI. The results
showed that (1) the binding of mAb 238 can be blocked by trypsin and that of mAb 217 by chymotrypsin; (2) the trypsin or chymotrypsin
inhibitory activities of BBI are blocked by mAb 238 or mAb 217, respectively; and (3) mAb 238 failed to recognize a tryptic
loop mutant BBI variant and mAb 217 was unable to bind a chymotryptic loop mutant BBI variant. These findings demonstrate
that the epitopes recognized by mAb 238 and mAb 217 reside, at least in part, in the tryptic and chymotryptic loops of BBI,
respectively. 相似文献
999.
Guilleaume B Buness A Schmidt C Klimek F Moldenhauer G Huber W Arlt D Korf U Wiemann S Poustka A 《Proteomics》2005,5(18):4705-4712
To process large numbers of samples in parallel is one potential of protein microarrays for research and diagnostics. However, the application of protein arrays is currently hampered by the lack of comprehensive technological knowledge about the suitability of 2-D and 3-D slide surface coatings. We have performed a systematic study to analyze how both surface types perform in combination with different fluorescent dyes to generate significant and reproducible data. In total, we analyzed more than 100 slides containing 1152 spots each. Slides were probed against different monoclonal antibodies (mAbs) and recombinant fusion proteins. We found two surface coatings to be most suitable for protein and antibody (Ab) immobilization. These were further subjected to quantitative analyses by evaluating intraslide and slide-to-slide reproducibilities, and the linear range of target detection. In summary, we demonstrate that only suitable combinations of surface and fluorescent dyes allow the generation of highly reproducible data. 相似文献
1000.
During the peri-implantation period, molecular signaling between embryo and endometrium (layer of tissue lining the uterus lumen) is supposed to be crucial for the maintenance of pregnancy. To investigate embryo-induced alterations in the proteome of bovine endometrium in the preattachment period (day 18), we used monozygotic cattle twins (generated by embryo splitting) as a model eliminating genetic variability as a source for proteome differences. One of the twins was pregnant after the transfer of two in vitro produced blastocysts, while the corresponding twin received a sham-transfer and served as a nonpregnant control. The two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) analysis of the endometrium samples of three twin pairs (pregnant/nonpregnant) revealed four proteins with significantly higher abundance (p < 10(-9)) in each sample derived from the pregnant animals: Rho GDP dissociation inhibitor beta; 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD); soluble NADP(+)-dependent isocitrate dehydrogenase 1; and acyl-CoA-binding protein. To verify the accuracy of the 2-D DIGE quantification, the abundances of 20 alpha-HSD were quantified by a targeted cleavable isotope-coded affinity tag (ICAT) approach. The mass spectrometry-based ICAT quantification matched perfectly the results obtained by 2-D DIGE quantification, demonstrating the accuracy of our data. These results demonstrate that our model (monozygotic twins) in combination with the appropriate analytical tools is particularly suitable for the detection of the proteins involved in the embryo-maternal interactions. 相似文献