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11.
Claudio Battilocchio Giovanna Poce Salvatore Alfonso Giulio Cesare Porretta Sara Consalvi Lidia Sautebin Simona Pace Antonietta Rossi Carla Ghelardini Lorenzo Di Cesare Mannelli Silvia Schenone Antonio Giordani Luigia Di Francesco Paola Patrignani Mariangela Biava 《Bioorganic & medicinal chemistry》2013,21(13):3695-3701
We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules. 相似文献
12.
Rigamonti D Bolognini D Mutti C Zuccato C Tartari M Sola F Valenza M Kazantsev AG Cattaneo E 《The Journal of biological chemistry》2007,282(34):24554-24562
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Lucarini Elena Micheli Laura Di Cesare Mannelli Lorenzo Ghelardini Carla 《Phytochemistry Reviews》2022,21(2):647-665
Phytochemistry Reviews - Investigation into glucosinolates (GLs) therapeutic effects boasts a long history, which began with the evidence that their hydrolysis-derived isothiocyanates (ITCs) could... 相似文献
15.
Giovanni Mantovani Vittorio Gebbia Mario Airoldi Cesare Bumma Paolo Contu Alessandro Bianchi Massimo Ghiani Daniela Dessì Elena Massa Luigi Curreli Biancarosa Lampis Paola Lai Carlo Mulas Antonio Testa Ernesto Proto Gabrio Cadeddu Giorgio Tore 《Cancer immunology, immunotherapy : CII》1998,47(3):149-156
We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical
response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2
(rIL-2) in patients with advanced (stage III–IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical
Al Sarraf treatment: 100 mg/m2 cisplatin i.v. on day 1 plus 1000 mg m−2 day−1 5-FU on days 1–5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8–12 and
15–19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study; 30 were evaluable
for toxicity and 28 for response. Seventeen patients were assigned to group A and 16 were assigned to group B. Three patients
(20%) of group A and 4 (31%) of group B had a complete response, 9 patients (60%) of group A and 6 (46%) of group B had a
partial response, with an overall response rate of 12 patients (80%) for group A and 10 patients (77%) for group B. Two patients
(13%) of group A and 3 patients (23%) group B had stable disease; 1 patient (7%) of group A had progressive disease. Thus,
there was not a statistically significant difference in response rate between the two groups and therefore there was no benefit
from the addition of immunotherapy with rIL-2 to the standard chemotherapy. Both regimens were well tolerated. There were
2 toxic deaths (6.7%), 1 from hematological causes in group A and 1 from cardiac causes in group B. Myelosuppression and gastrointestinal
toxicity, mainly nausea/vomiting and stomatitis, were the most frequent toxicities. The calculated number of patients for
the sample has not yet been reached; however, the projection of our present results suggests that it is highly improbable
that a clinically significant difference between the two treatment groups will be observed even if the calculated patient
sample size is achieved.
Received: 9 April 1998 / Accepted: 30 June 1998 相似文献
16.
Oppedisano F Fanello D Calvani M Indiveri C 《Journal of biochemical and molecular toxicology》2008,22(1):8-14
The interaction of mildronate [3-(2,2,2-trimethylhydrazine) propionate] with the purified mitochondrial carnitine/acylcarnitine transporter reconstituted in liposomes has been studied. Mildronate, externally added to the proteoliposomes, strongly inhibited the carnitine/carnitine antiport catalyzed by the reconstituted transporter with an IC(50) of 560 muM. A kinetic analysis revealed that the inhibition is completely competitive, that is, mildronate interacts with the substrate-binding site. The half-saturation constant of the transporter for external mildronate (K(i)) is 530 muM. Carnitine/mildronate antiport has been measured as [(3)H]carnitine uptake into proteoliposomes containing internal mildronate or as [(3)H]carnitine efflux from proteoliposomes in the presence of external mildronate, indicating that mildronate is transported by the carnitine/acylcarnitine transporter and that the inhibition observed was due to the transport of mildronate in the place of carnitine. The intraliposomal half-saturation constant for mildronate transport (K(m)) has been determined. Its value, 18 mM, is much higher than the external half-saturation constant (K(i)) in agreement with the asymmetric properties of the transporter. In vivo, the antiport reaction between cytosolic (administered) mildronate and matrix carnitine may cause intramitochondrial carnitine depletion. This effect, together with the inhibition of the physiological transport, will lead to impairment of fatty acid utilization. 相似文献
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Clorinda Schettino Maria A Bareschino Paolo Maione Antonio Rossi Fortunato Ciardiello Cesare Gridelli 《Current Genomics》2008,9(4):252-262
Although notable progress has been made in the treatment of non-small-cell lung cancer (NSCLC) in recent years, this disease is still associated with a poor prognosis. Despite early-stage NSCLC is considered a potentially curable disease following complete resection, the majority of patients relapse and eventually die after surgery. Adjuvant chemotherapy prolongs survival, altough the absolute improvement in 5-year overall survival is only approximately 5%.Trying to understand the role of genes which could affect drug activity and response to treatment is a major challenge for establishing an individualised chemotherapy according to the specific genetic profile of each patient. Among genes involved in the DNA repair system, the excision repair cross-complementing 1 (ERCC1) is a useful markers of clinical resistance to platinum-based chemotherapy. In the International Lung Cancer Trial (IALT) adjuvant chemotherapy significantly prolonged survival among patients with ERCC1 negative tumors but not among ERCC1-positive patients. BRCA1 and ribonucleotide reductase M1 (RRM1), two other key enzymes in DNA synthesis and repair, appear to be modulators of drug sensitivity and may provide additional information for customizing adjuvant chemotherapy.Several clinical trials suggest that overexpression of class III β-tubulin is an adverse prognostic factor in cancer since it could be responsible for resistance to anti-tubulin agents. A retrospective analysis of NCIC JBR.10 trial showed that high tubulin III expression is associated with a higher risk of relapse following surgery alone but also with a higher probability of benefit from adjuvant cisplatin plus vinorelbine chemotherapy.Finally, the use of gene expression patterns such as the lung metagene model could provide a potential mechanism to refine the estimation of a patient’s risk of disease recurrence and could affect treatment decision in the management of early stage of NSCLC.In this review we will discuss the potential role of pharmacogenomic approaches to guide the medical treatment of early stage NSCLC.Key Words: NSCLC, adjuvant treatment, molecular markers, ERCC1, RRM1, β-tubulin, EGFR. 相似文献
19.
Arresta E Bernardini S Gargioli C Filoni S Cannata SM 《Journal of experimental zoology. Part A, Comparative experimental biology》2005,303(1):1-12
In larval X. laevis the capacity to regenerate a lens under the influence of inductive factors present in the vitreous chamber is restricted to the outer cornea and pericorneal epidermis (Lentogenic Area, LA). However, in early embryos, the whole ectoderm is capable of responding to inductive factors of the larval eye forming lens cells. In a previous paper, Cannata et al. (2003) demonstrated that the persistence of lens-forming competence in the LA is the result of early signals causing lens-forming bias in the presumptive LA and of late signals from the eye causing cornea development. This paper analyzes 1) the decrease of the lens-forming capacity in ectodermal regions both near LA (head epidermis) and far from LA (flank epidermis) during development, 2) the capacity of the head epidermis and flank epidermis to respond to lens-competence promoting factors released by an eye transplanted below these epidermal regions, and 3) the eye components responsible for the promoting effect of the transplanted eye. Results were obtained by implanting fragments of ectoderm or epidermis into the vitreous chamber of host tadpoles and by evaluating the percentage of implants positive to a monoclonal antibody anti-lens. These results demonstrated that the lens-forming competence in the flank region is lost at the embryonic stage 30/31 and is weakly restored by eye transplantation; however, lens-forming competence in the head region is lost at the larval stage 48 and is strongly restored by eye transplantation. The authors hypothesize that during development the head ectoderm outside the LA is attained by low levels of the same signals that attain the LA and that these signals are responsible for the maintenance of lens-forming competence in the cornea and pericorneal epidermis of the larva. In this hypothesis, low levels of these signals slacken the decrease of the lens-forming competence in the head ectoderm and make the head epidermis much more responsive than the flank epidermis to the effect of promoting factors released by a transplanted eye. Results obtained after transplantation of eyes deprived of some components indicate that the lens and the retina are the main source of these promoting factors. The immunohistochemical detection of the FGFR-2 (bek variant) protein in the epidermis of stage 53 larvae submitted to eye transplantation at stage 46 showed that the eye transplantation increased the level of FGFR-2 protein in the head epidermis but not in the flank epidermis, indicating that the lens-forming competence in X. laevis epidermis could be related to the presence of an activated FGF receptor system in the responding tissue. 相似文献
20.