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71.
Batista Dda G Batista MM de Oliveira GM Britto CC Rodrigues AC Stephens CE Boykin DW Soeiro Mde N 《PloS one》2011,6(7):e22155
Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via i.p. route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals. 相似文献
72.
Ana Carolina Luchiari Cristiane Regina do Amaral Duarte Fúlvio Aurélio de Morais Freire Kari Nissinen 《Journal of Ethology》2007,25(2):169-175
We studied the colour preference of isolated Nile tilapia (Oreochromis niloticus) and whether previous residence or body size can affect environmental colour choice. In the first phase, a cylindrical tank
was divided into five differently coloured compartments (yellow, blue, green, white and red), a single fish was introduced
into the tank and the frequency at which this fish visited each compartment was recorded over a 2-day study period. An increasingly
larger fish (approx +2 cm in length each time) was then added into the tank on each of days 3, 5 and 7 (=four fish in the
tank by day 7), and the frequency at which each fish visited the different compartments of the tank was observed twice a day
to obtain visit frequency data on the differently sized fishes. This experiment was replicated six times. In the first phase,
the solitary fish established residence inside the yellow compartment on the first and second days. Following the
introduction of a larger fish, the smaller fish was displaced from the occupied compartment. Nile tilapia possibly shows this
preference for yellow as a function of its visual spectral sensitivity and/or the spectral characteristics of its natural
environment. Moreover, body size is an important factor in determining hierarchical dominance and territorial defence, and
dominant fish chose the preferred environmental colour compartment as their territory. 相似文献
73.
Mycobacterium tuberculosis (Mtb) is thought to preferentially rely on fatty acid metabolism to both establish and maintain chronic infections. Its metabolic network, however, allows efficient co-catabolism of multiple carbon substrates. To gain insight into the importance of carbohydrate substrates for Mtb pathogenesis we evaluated the role of glucose phosphorylation, the first reaction in glycolysis. We discovered that Mtb expresses two functional glucokinases. Mtb required the polyphosphate glucokinase PPGK for normal growth on glucose, while its second glucokinase GLKA was dispensable. 13C-based metabolomic profiling revealed that both enzymes are capable of incorporating glucose into Mtb''s central carbon metabolism, with PPGK serving as dominant glucokinase in wild type (wt) Mtb. When both glucokinase genes, ppgK and glkA, were deleted from its genome, Mtb was unable to use external glucose as substrate for growth or metabolism. Characterization of the glucokinase mutants in mouse infections demonstrated that glucose phosphorylation is dispensable for establishing infection in mice. Surprisingly, however, the glucokinase double mutant failed to persist normally in lungs, which suggests that Mtb has access to glucose in vivo and relies on glucose phosphorylation to survive during chronic mouse infections. 相似文献
74.
Pauline M. Leite Rodrigo S. Gomes Amanda B. Figueiredo Tiago D. Serafim Wagner L. Tafuri Carolina C. de Souza Sandra A. L. Moura Juliana L. R. Fietto Maria N. Melo Fátima Ribeiro-Dias Milton A. P. Oliveira Ana Rabello Luís C. C. Afonso 《PLoS neglected tropical diseases》2012,6(10)
Background
Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease.Methodology/Principal Findings
Our results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages.Conclusions/Significance
Our data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important factor in determining the clinical outcome of leishmaniasis. 相似文献75.
Yasmin Silva Rizk Alice Fischer Marillin de Castro Cunha Patrik Oening Rodrigues Maria Carolina Silva Marques Maria de Fátima Cepa Matos M?nica Cristina Toffoli Kadri Carlos Alexandre Carollo Carla Cardozo Pinto de Arruda 《Memórias do Instituto Oswaldo Cruz》2014,109(8):1050-1056
This study is the first phytochemical investigation of Selaginella sellowii
and demonstrates the antileishmanial activity of the hydroethanolic extract
from this plant (SSHE), as well as of the biflavonoids amentoflavone and
robustaflavone, isolated from this species. The effects of these substances were
evaluated on intracellular amastigotes of Leishmania (Leishmania)
amazonensis, an aetiological agent of American cutaneous leishmaniasis.
SSHE was highly active against intracellular amastigotes [the half maximum inhibitory
concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation
of the two bioflavonoids with the highest activity: amentoflavone, which was about
200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and
3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index
(SI) (22 and 30), robustaflavone, which was also active against L.
amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5
µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells.
The production of nitric oxide (NO) was lower in cells treated with amentoflavone
(suggesting that NO does not contribute to the leishmanicidal mechanism in this
case), while NO release was higher after treatment with robustaflavone. S.
sellowii may be a potential source of biflavonoids that could provide
promising compounds for the treatment of cutaneous leishmaniasis. 相似文献
76.
Rafaela Magalhães Brandão Maria das Graças Cardoso Luís Roberto Batista Alex Rodrigues Silva Caetano Ana Carolina Cortez Lemos Maria Alice Martins David Lee Nelson Juliano Elvis De Oliveira 《Letters in applied microbiology》2022,74(5):765-776
Poly(lactic acid) (PLA) nanofibres containing different proportions of the essential oils from Ocimum basilicum L. and Ocimum gratissimum L. were prepared by solution blow spinning method. The essential oils were extracted by hydrodistillation and characterized by gas chromatography. MEV, contact angle, DSC and FTIR were used to characterize the nanofibres. The effect of bioative nanofibres on the growth of the fungus and on the production of ochratoxin A were evaluated using the fumigation test. Linalool, 1·8-cineole and camphor were the principal components of the essential oil from O. basilicum, and eugenol was the principal constituent in the oil from O. gratissimum. An increase in the average diameter of the nanofibres was observed with the addition of the essential oils. The essential oils acted as a plasticizer, resulting in a reduction in the crystallinity of the PLA. The encapsulation of essential oils in PLA nanofibres was verified by FTIR. An effective antifungal and antimicotoxygenic activity against Aspergillus ochraceus and Aspergillus westerdjikiae was observed for the bioative nanofibres. These results confirm the potential of PLA nanofibres containing the essential oils for the control of toxigenic fungi that cause the deterioration of food and are harmful to human health. 相似文献
77.
Livia Garzia Noriyuki Kijima A. Sorana Morrissy Pasqualino De Antonellis Ana Guerreiro-Stucklin Borja L. Holgado Xiaochong Wu Xin Wang Michael Parsons Kory Zayne Alex Manno Claudia Kuzan-Fischer Carolina Nor Laura K. Donovan Jessica Liu Lei Qin Alexandra Garancher Kun-Wei Liu Michael D. Taylor 《Cell》2018,172(5):1050-1062.e14
78.
79.
80.
Jos C. E. Serrano Juan Antonio Baena‐Fustegueras Meritxell Martin‐Gari Helene Rassendren Anna Cassanye Alba Naudí Carolina Lpez‐Cano Enric Snchez María Cruz de la Fuente‐Jurez Fernando Herrerías Gonzlez Jorge J. Olsina Kissler Albert Lecube Manuel Portero‐Otín 《Obesity (Silver Spring, Md.)》2019,27(7):1133-1140