全文获取类型
收费全文 | 2281篇 |
免费 | 106篇 |
国内免费 | 10篇 |
专业分类
2397篇 |
出版年
2023年 | 44篇 |
2022年 | 61篇 |
2021年 | 87篇 |
2020年 | 55篇 |
2019年 | 68篇 |
2018年 | 84篇 |
2017年 | 68篇 |
2016年 | 89篇 |
2015年 | 128篇 |
2014年 | 119篇 |
2013年 | 166篇 |
2012年 | 199篇 |
2011年 | 202篇 |
2010年 | 108篇 |
2009年 | 97篇 |
2008年 | 95篇 |
2007年 | 110篇 |
2006年 | 95篇 |
2005年 | 81篇 |
2004年 | 51篇 |
2003年 | 52篇 |
2002年 | 44篇 |
2001年 | 25篇 |
2000年 | 21篇 |
1999年 | 23篇 |
1998年 | 15篇 |
1997年 | 5篇 |
1995年 | 14篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1989年 | 9篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 15篇 |
1985年 | 7篇 |
1984年 | 9篇 |
1983年 | 10篇 |
1982年 | 5篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 10篇 |
1972年 | 8篇 |
1971年 | 10篇 |
排序方式: 共有2397条查询结果,搜索用时 0 毫秒
91.
Andrzej Myśliwski Jolanta Myśliwska Zbigniew Kmieć 《Histochemistry and cell biology》1977,52(1):91-96
Summary A comparsion of the Feulgen hydrolysis curves and the chromatin compactness of the liver cell nuclei of young and old rats was made. It was found that the rate of DNA depurination and chromatin compactness are higher in the liver cell nuclei of old rats, both in di-and tetraploidal cells. The effect of fixation upon the course of the hydrolysis curves is discussed.This investigation was supported by grant 474/VI Committee of Cell Pathology, Polish Academy of Sciences 相似文献
92.
93.
Imola Wilhelm Péter Nagyőszi Attila E. Farkas Pierre‐Olivier Couraud Ignacio A. Romero Babette Weksler Csilla Fazakas Ngo Thi Khue Dung Sándor Bottka Hannelore Bauer Hans‐Christian Bauer István A. Krizbai 《Journal of neurochemistry》2008,107(1):116-126
Because of the relative impermeability of the blood‐brain barrier (BBB), many drugs are unable to reach the CNS in therapeutically relevant concentration. One method to deliver drugs to the CNS is the osmotic opening of the BBB using mannitol. Hyperosmotic mannitol induces a strong phosphorylation on tyrosine residues in a broad spectrum of proteins in cerebral endothelial cells, the principal components of the BBB. Previously, we have shown that among targets of tyrosine phosphorylation are β‐catenin, extracellular signal‐regulated kinase 1/2 and the non‐receptor tyrosine kinase Src. The aim of this study was to identify new signalling pathways activated by hypertonicity in cerebral endothelial cells. Using an antibody array and immunoprecipitation we identified the receptor tyrosine kinase Axl to become tyrosine phosphorylated in response to hyperosmotic mannitol. Besides activation, Axl was also cleaved in response to osmotic stress. Degradation of Axl proved to be metalloproteinase‐ and proteasome‐dependent and resulted in 50–55 kDa C‐terminal products which remained phosphorylated even after degradation. Specific knockdown of Axl increased the rate of apoptosis in hyperosmotic mannitol‐treated cells; therefore, we assume that activation of Axl may be a protective mechanism against hypertonicity‐induced apoptosis. Our results identify Axl as an important element of osmotic stress‐induced signalling. 相似文献
94.
Katja Petzold Diane Poster Fabienne Krauer Katharina Spanaus Gustav Andreisek Thi Dan Linh Nguyen-Kim Ivana Pavik Thien Anh Ho Andreas L. Serra Laura Rotar 《PloS one》2015,10(4)
Background
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course.Methods
ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results.Results
In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found.Conclusion
UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable. Further studies are needed to evaluate the property of the aforementioned biomarkers to assess disease state at early ADPKD stage. 相似文献95.
Heparin binding to the urokinase kringle domain. 总被引:5,自引:0,他引:5
R W Stephens A M Bokman H T My?h?nen T Reisberg H Tapiovaara N Pedersen J Gr?ndahl-Hansen M Llinás A Vaheri 《Biochemistry》1992,31(33):7572-7579
The binding of urokinase to immobilized heparin and dextran sulfate was studied using activity assays of the bound urokinase. The markedly higher binding observed with high M(r) urokinase compared to low M(r) urokinase indicated a role for the amino-terminal fragment (ATF). This was confirmed by the use of inactive truncated urokinase and monoclonal antibodies specific for the ATF in competition assays of urokinase binding. Antibody competition assays suggested a site in the kringle domain, and a synthetic decapeptide Arg-52-Trp-62 from the kringle sequence (kringle numbering convention) was competitive in assays of urokinase binding to dextran sulfate and heparin. Heparin binding to the urokinase kringle was unambiguously demonstrated via 1H NMR spectroscopy at 500 MHz. Effective equilibrium association constants (K(a)*) were determined for the interaction of isolated kringle fragment and low M(r) heparin at pH 7.2. The binding was strong in salt-free 2H2O (K(a)* approximately 57 mM-1) and remained significant in 0.15 M NaCl (K(a)* approximately 12 mM-1), supporting a potential physiological role for the interaction. This is the first demonstration of a function for the kringle domain of urokinase, and it suggests that while the classical kringle structure has specificity for lysine binding, there may also exist a class of kringles with affinity for polyanion binding. 相似文献
96.
97.
Thi Thuy Tran Gashaw Mamo Bo Mattiasson Rajni Hatti-Kaul 《Journal of industrial microbiology & biotechnology》2010,37(3):279-287
Phytase is used as a feed additive for degradation of antinutritional phytate, and the enzyme is desired to be highly thermostable
for it to withstand feed formulation conditions. A Bacillus sp. MD2 showing phytase activity was isolated, and the phytase encoding gene was cloned and expressed in Escherichia coli. The recombinant phytase exhibited high stability at temperatures up to 100°C. A higher enzyme activity was obtained when
the gene expression was done in the presence of calcium chloride. Production of the enzyme by batch- and fed-batch cultivation
in a bioreactor was studied. In batch cultivation, maintaining dissolved oxygen at 20–30% saturation and depleting inorganic
phosphate below 1 mM prior to induction by IPTG resulted in over 10 U/ml phytase activity. For fed–batch cultivation, glucose
concentration was maintained at 2–3 g/l, and the phytase expression was increased to 327 U/ml. Induction using lactose during
fed-batch cultivation showed a lag phase of 4 h prior to an increase in the phytase activity to 71 U/ml during the same period
as IPTG-induced production. Up to 90% of the total amount of expressed phytase leaked out from the E. coli cells in both IPTG- and lactose-induced fed-batch cultivations. 相似文献
98.
B.u.i. Van Le Maria H. Cruz de Carvalho Yasmine Zuily-Fodil Anh T. Pham Thi Kiem Tran Thanh Van 《Journal of plant physiology》2002,159(11)
A simple protocol was established for high frequency direct shoot regeneration of cowpea [Vigna unguiculata (L.) cv. EPACE-1]. Bud proliferation occurred at the cotyledonary nodes of cowpea seedlings three weeks after culture on a medium containing Murashige and Skoog salts (1962) and B5 vitamins (Gamborg et al. 1968) supplemented with TDZ. A 10 μmol/L TDZ pre-treatment, shoot tip removal and excision of longitudinal thin cell layers (TCL) at the level of the cotyledonary nodes with subsequent culture on a MSB5 medium supplemented with 1 μmol/L IBA and 1 μmol/L TDZ were the optimal conditions for maximum bud proliferation. Up to 32.5 regenerated shoot buds were produced per TCL. The regenerated plants (R0) were true-to-type and successfully transferred to soil. 相似文献
99.
Huy NT Serada S Trang DT Takano R Kondo Y Kanaori K Tajima K Hara S Kamei K 《Journal of biochemistry》2003,133(5):693-698
Plasmodium falciparum histidine-rich protein 2 (PfHRP2) has been suggested to be an initiator of the polymerization of heme, which is produced as by-product on the digestion of hemoglobin, and a promoter of the H(2)O(2)-induced degradation of heme in food vacuoles of the malarial parasite. In this work, we have designed PfHRP2 model peptides, R18 and R27 (18 and 27 residues, respectively), and used them for optical and electron spin resonance spectroscopic measurements to confirm that the axial ligands of the heme-PfHRP2 complex are the nitrogenous donors derived from the imidazole moieties of histidine residues of PfHRP2. In addition, we revealed that the affinities of R18 and R27 for heme (K(d) = 2.21 x 10(-6) M and 0.71 x 10(-6) M, respectively) might be as high as that of PfHRP2 (K(d) = 0.94 x 10(-6) M). The R27 peptide can remove heme from membrane-intercalated heme and inhibit heme-induced hemolysis. Therefore, we suggest another function of PfHRP2: it may play an important role in the neutralization of toxic heme in the parasite cytoplasm and infected erythrocytes by removing heme from heme-bound membranes or reducing heme-induced hemolysis. 相似文献
100.
Kmieć Z Kotlarz G Myśliwski A Wyrzykowska M Pokrywka L 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2002,40(2):185-186
Age-related alterations in the structure and function of many organs often become apparent under stimulation of their function. Although the ageing process affects the regulation of mineral homeostasis, the function of thyroid C-cells that secrete calcitonin (CT) under the conditions of fasting and refeeding, a way of dietary manipulation that reveal the existence of age-related changes of follicular thyroid cells, has not been characterized. Therefore, we investigated the number of C-cells and serum CT concentration in young (4 mo) and old (26 mo) male rats fasted for 48 hours, and then refed for 4 or 24 hours. We found significantly higher number of C-cells in thyroids of old vs young rats both under basal conditions, and after fasting/refeeding. Correspondingly, serum calcitonin level was higher in fed or fasted old rats vs young ones. However, in young rats refeeding decreased, whereas in old animals increased serum concentrations of calcitonin. Thus, the control of serum calcium concentration, that was well preserved in old rats, occurs at the expense of increased serum CT level both under basal conditions, and after refeeding. These observations suggest that C-cell function is altered in ageing. 相似文献