全文获取类型
收费全文 | 5577篇 |
免费 | 342篇 |
专业分类
5919篇 |
出版年
2023年 | 13篇 |
2022年 | 66篇 |
2021年 | 107篇 |
2020年 | 71篇 |
2019年 | 82篇 |
2018年 | 123篇 |
2017年 | 106篇 |
2016年 | 172篇 |
2015年 | 263篇 |
2014年 | 268篇 |
2013年 | 430篇 |
2012年 | 491篇 |
2011年 | 427篇 |
2010年 | 247篇 |
2009年 | 252篇 |
2008年 | 313篇 |
2007年 | 321篇 |
2006年 | 280篇 |
2005年 | 273篇 |
2004年 | 272篇 |
2003年 | 267篇 |
2002年 | 228篇 |
2001年 | 47篇 |
2000年 | 43篇 |
1999年 | 51篇 |
1998年 | 55篇 |
1997年 | 36篇 |
1996年 | 51篇 |
1995年 | 33篇 |
1994年 | 50篇 |
1993年 | 22篇 |
1992年 | 40篇 |
1991年 | 31篇 |
1990年 | 27篇 |
1989年 | 23篇 |
1988年 | 22篇 |
1987年 | 18篇 |
1986年 | 16篇 |
1985年 | 20篇 |
1984年 | 32篇 |
1983年 | 18篇 |
1982年 | 26篇 |
1981年 | 22篇 |
1980年 | 22篇 |
1979年 | 11篇 |
1978年 | 17篇 |
1977年 | 16篇 |
1976年 | 17篇 |
1975年 | 15篇 |
1973年 | 15篇 |
排序方式: 共有5919条查询结果,搜索用时 0 毫秒
91.
92.
Basolateral Ca2+-dependent K+-channels play a key role in Cl- secretion induced by taurodeoxycholate from colon mucosa 总被引:1,自引:0,他引:1
Moschetta A Portincasa P Debellis L Petruzzelli M Montelli R Calamita G Gustavsson P Palasciano G 《Biology of the cell / under the auspices of the European Cell Biology Organization》2003,95(2):115-122
The diarrhea associated with malabsorption of bile salts such as the secondary hydrophobic taurodeoxycholate (TDC) may be partly explained by the TDC-induced increase in colon Cl(-) secretion. We, therefore, investigated the effects of TDC (0.5-8 mM) on electrical parameters and electrolyte transport of rat proximal colon mucosa mounted in Ussing chambers. Colonic secretion, measured as short circuit current (I(SC)), progressively increased on mucosal incubation with TDC ranging 0.5-2 mM; up to TDC 2 mM, a spontaneous recovery toward control values with no changes in epithelial resistance (Rt), and lactate dehydrogenase (LDH) release was observed. In contrast, for TDC > 2 mM, I(SC) increased further and the effect was progressive and associated with a significant decrease in the Rt and increased LDH release, implying a cytolytic effect. Mucosal preincubation with the Cl(-) channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), fully prevented the precytolytic effect of TDC on I(SC). Serosal preincubation with furosemide, a Na(+)/K(+)/2Cl(-) cotransporter inhibitor, significantly reduced TDC-induced increase in I(SC). Inhibition of the basolateral Ca(2+)-dependent K(+) channel-rSK4-with serosal clotrimazole or incubation with mucosal Ca(2+)-free (EGTA) buffer completely prevented precytolytic TDC-induced increase in I(SC). In conclusion, Cl(-) secretion is activated in colon mucosa by TDC low concentrations; while at higher concentrations, a detergent cytotoxic effect intervenes. Activation of the Ca(2+)-dependent basolateral K(+) pathway, through TDC-induced apical Ca(2+) influx, provides the Na(+)/K(+)/2Cl(-) basolateral activation, thereby the driving force for the apical exit of Cl(-) ions. These findings further enhance the knowledge of the pathogenic mechanisms of diarrhea associated with bile salt malabsorption. 相似文献
93.
Hildur Helgadottir Emilia Andersson Lisa Villabona Lena Kanter Henk van der Zanden Geert W. Haasnoot Barbara Seliger Kjell Bergfeldt Johan Hansson Boel Ragnarsson-Olding Rolf Kiessling Giuseppe Valentino Masucci 《Cancer immunology, immunotherapy : CII》2009,58(10):1599-1608
Purpose We have previously demonstrated an association of the human leukocyte antigen (HLA), HLA-A2 allele with ovarian and prostate
cancer mortality as well as a segregation of the ancestral HLA haplotype (AHH) 62.1 [(A2) B15 Cw3 DRB1*04] in patients with
stage III–IV serous ovarian cancer. The objective of the present study was to determine the role of the HLA phenotype on the
prognosis in stage III–IV malignant melanoma patients.
Patients and methods A cohort of metastatic malignant melanoma patients (n = 91), in stage III (n = 26) or IV (n = 65) were analysed for HLA-A, -B, -Cw and -DRB1 types by PCR/sequence-specific primer method. The frequencies of HLA alleles
in the patients were compared to that of healthy Swedish bone marrow donors. The effect of HLA types on prognosis was defined
by Kaplan–Meier and Cox analysis.
Results The presence of the AHH 62.1 in clinical stage IV patients was significantly and independently associated with the worst survival
rate recorded from the appearance of metastasis (HR = 2.14; CI = 1.02–4.4; P = 0.04). In contrast, the period from the primary diagnosis to metastasis was the longest in patients with this haplotype
(HR = 0.40; CI = 0.17–0.90; P = 0.02).
Conclusions Melanoma patients in our cohort with 62.1 AHH which is associated with autoimmune diseases have an initial strong anti-tumour
control with longer metastasis-free period. These patients have rapid progression after the appearance of metastasis, responding
poorly to chemo- or/and immunotherapy. This apparently paradoxical clinical process could be due to the interplay between
tumour clones escape and immune surveillance ending up with a rapid disease progression.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
94.
de Giuseppe PO Ullah A Silva DT Gremski LH Wille AC Chaves Moreira D Ribeiro AS Chaim OM Murakami MT Veiga SS Arni RK 《Biochemical and biophysical research communications》2011,409(4):6064-627
Phospholipases D (PLDs) are principally responsible for the local and systemic effects of Loxosceles envenomation including dermonecrosis and hemolysis. Despite their clinical relevance in loxoscelism, to date, only the SMase I from Loxosceles laeta, a class I member, has been structurally characterized. The crystal structure of a class II member from Loxosceles intermedia venom has been determined at 1.7 Å resolution. Structural comparison to the class I member showed that the presence of an additional disulphide bridge which links the catalytic loop to the flexible loop significantly changes the volume and shape of the catalytic cleft. An examination of the crystal structures of PLD homologues in the presence of low molecular weight compounds at their active sites suggests the existence of a ligand-dependent rotamer conformation of the highly conserved residue Trp230 (equivalent to Trp192 in the glycerophosphodiester phosphodiesterase from Thermus thermophofilus, PDB code: 1VD6) indicating its role in substrate binding in both enzymes. Sequence and structural analyses suggest that the reduced sphingomyelinase activity observed in some class IIb PLDs is probably due to point mutations which lead to a different substrate preference. 相似文献
95.
96.
Virginia Sanchini Giuseppina Bonizzi Davide Disalvatore Massimo Monturano Salvatore Pece Giuseppe Viale Pier Paolo Di Fiore Giovanni Boniolo 《Bioethics》2016,30(4):260-271
Traditional Informed Consent is becoming increasingly inadequate, especially in the context of research biobanks. How much information is needed by patients for their consent to be truly informed? How does the quality of the information they receive match up to the quality of the information they ought to receive? How can information be conveyed fairly about future, non‐predictable lines of research? To circumvent these difficulties, some scholars have proposed that current consent guidelines should be reassessed, with trust being used as a guiding principle instead of information. Here, we analyse one of these proposals, based on a Participation Pact, which is already being offered to patients at the Istituto Europeo di Oncologia, a comprehensive cancer hospital in Milan, Italy. 相似文献
97.
98.
Flavio Massimo Garlaschi Giuseppe Zucchelli Robert Charles Jennings 《Photosynthesis research》1989,20(3):207-220
An experimental analysis is presented concerning the effect on relative light absorption by the two photosystems caused by (a) a highly light scattering environment (the detour effect) and (b) light filtration across successive chloroplast layers (the light attenuation effect). Both suspensions of isolated chloroplasts and leaves were employed.It is concluded that within a single spinach leaf these phenomena are likely to lead to only rather small increases in relative photosystem I absorption and activity with respect to photosystem II and will thus not exert a significant effect on non cyclic electron transport. On the contrary when light is filtrated across successive vegetation layers (shade light) significant increases in the relative PSI absorption and activity may be encountered.It is determined that the detour effect in mature leaves from a variety of plants increases overall photosynthetically useful light absorption by 35–40%.Abbreviations FM
maximal fluorescence
- LHCP2
light-harvesting chlorophyl a/b protein complex II
- QA-primary
quinone acceptor of photosystem II 相似文献
99.
The kinetics of LHCP phosphorylation and associated changes in photosystem cross-section and energy ‘spill-over’ from PS II to PS I have been examined in isolated spinach chloroplasts. During an initial phosphorylation period of 3–6 min, in the presence of saturating concentrations of Mg2+, the increase in PS I and decrease in PS II cross-section are largely completed, as judged by both measurements of the steady-state redox state of Q and fluorescence yield changes. This corresponds to a period of rapid 32P incorporation into the low-molecular weight LHCP polypeptide. Subsequent to this initial 3–6-min period there is substantial further phosphorylation of both LHCP polypeptides, which is not accompanied by significant changes in photosystem cross-section, even after the chloroplasts had been unstacked with extensive mixing of PS I and PS II by Mg-removal. It is suggested that there exists a specific ‘mobile’ population of LHCP molecules which is rapidly phosphorylated and which may be enriched in the low-molecular-weight polypeptide. In addition, measurements of the kinetics of the ‘spill-over’ changes upon either Mg2+ addition or removal indicate that the continued phosphorylation of LHCP is able to increase the ‘spill-over’ process under favourable ionic conditions. 相似文献
100.
Chemical Profile and Antioxidant Properties of Extracts and Essential Oils from Citrus × limon (L.) Burm. cv. Femminello Comune 下载免费PDF全文
Monica Rosa Loizzo Rosa Tundis Marco Bonesi Giuseppe Di Sanzo Alessandra Verardi Catia Giovanna Lopresto Alessandro Pugliese Francesco Menichini Roberto Balducchi Vincenza Calabrò 《化学与生物多样性》2016,13(5):571-581
Citrus × limon cv. Femminello Comune (Rutaceae) from Rocca Imperiale (Italy), one of the six Protected Geographical Indication (PGI) Italian lemon crops, has been recently received renewed interest. In this work, fresh and dried peels and leaves were extracted by hydrodistillation, supercritical fluid extraction (SFE), and Soxhlet apparatus. Chemical profile was assessed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). Except for leaves extracts obtained by Soxhlet apparatus, the monoterpene hydrocarbons fraction dominated. Limonene, γ‐terpinene, and β‐pinene were the main identified compounds. The antioxidant activity was investigated using different in vitro assays namely 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), ABTS, ferric reducing ability power (FRAP), and β‐carotene bleaching test. In DPPH test, the essential oil obtained by hydrodistillation of fresh peel exhibited the highest activity (IC50 of 1.17 mg/ml). Leaves extracted by SFE showed a good activity in both DPPH and β‐carotene bleaching test with IC50 values of 2.20 and 6.66 mg/ml, respectively. Monoterpene hydrocarbons fraction exhibited a positive Pearson's correlation coefficient with all antioxidant assays. Leaves, often considered waste material, should be considered from a different point because they represent a matrix of indisputable interest. 相似文献